A Pilot Study to Assess the Effects of a Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) Therapy on Re-hospitalization in Patients With Sleep-Disordered Breathing With Co-morbid COPD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study to Assess the Effects of a Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) Therapy on Re-hospitalization in Patients With Sleep-Disordered Breathing With Co-morbid COPD (NCT02446769), a randomized na study. The primary outcome is Number of Participants Enrolled Requiring Emergent Healthcare (Such as Re-hospitalization, Unscheduled Physician Office Visits, Urgent Care Visits or Emergency Room Visits)..

2. Clinical Question

3. Trial Design

This was a randomized, multi-center, open-label, parallel-group pilot study. Random allocation was recorded, masking was listed as none, and the registry phase was recorded as NA. The stated enrollment was 18. The study status is terminated. Its recorded start date was 2017-10-06, and its primary completion date was 2018-05-03. The sponsor was Philips Respironics.

The intervention arm received AVAPS-AE non-invasive ventilation therapy, with the arm description specifying initiation for 60 days. The standard-care group was to receive evaluation and treatment for sleep-disordered breathing according to the participant’s health care provider’s usual care pathway. The record does not report details of the randomization sequence, allocation concealment, site count, or reasons for termination.

The primary outcome was assessed at 60 days post-discharge and concerned the number of participants requiring emergent healthcare. Secondary outcomes listed in the registry include healthcare costs; changes in SF-36 and FOSQ quality-of-life measures at 30 and 60 days; a composite time-to-occurrence outcome for non-emergent healthcare utilization; time to re-hospitalization alone; and hospitalizations over 3 years for participants optionally enrolled in a registry. The record lists six secondary outcomes and eight outcome measures overall.

For the primary outcome, the posted arm results are one participant in the AVAPS-AE group and zero participants in the standard-care group, with arm counts of three and two, respectively. These outcome counts do not account for the stated enrollment of 18; the reason for the difference is not reported in the registry record. No comparative analysis is reported.

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.

Screening Period

Reasons for not completing this period:

Study Period

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: Due to the low enrollment, and low number of participants randomized into the study baseline analysis population description data was combined to provide more purposeful data.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Enrolled Requiring Emergent Healthcare (Such as Re-hospitalization, Unscheduled Physician Office Visits, Urgent Care Visits or Emergency Room Visits)., measured over 60 days post-discharge.

The primary endpoint counts participants who required emergent healthcare during the 60 days post-discharge. The outcome title gives examples: re-hospitalization, unscheduled physician office visits, urgent care visits, and emergency room visits. Its description refers to emergent and non-emergent healthcare utilization, so the precise boundary between included events is not fully clear from the record.

The endpoint is a participant count, rather than a count of all healthcare visits. In general, a participant-level event outcome can record whether each participant experienced at least one qualifying event during follow-up. That distinction matters because repeated visits by one participant and events in separate participants are different patterns, even if an overall event count were the same. The registry record does not explain how multiple events for one participant were handled.

Healthcare use was the focus because the study sought to assess re-hospitalization and other healthcare utilization after discharge. The endpoint could therefore capture use beyond re-hospitalization alone, according to its examples. It does not, by itself, describe the severity, reason, or clinical consequences of each event. The posted primary endpoint results record one participant with an event in the AVAPS-AE arm and zero in standard care. The registry record does not report a statistical comparison or further event-level detail.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary endpoint is recorded as a binary outcome: participants with an event, represented by counts. In general, binary outcomes classify each participant according to whether a defined event occurred during the specified follow-up. Here, the event definition concerns emergent healthcare, with examples including re-hospitalization and unscheduled visits. The count is not the same as the number of visits or events, and the registry record does not say how repeat events for one participant were handled.

What does a two-arm comparison require? A comparison between randomized groups ordinarily estimates how outcomes differ between the intervention and comparator groups. The estimate can be expressed in different ways, depending on the prespecified statistical approach. The registry record does not report an analysis plan or an estimable comparative result for this endpoint. It explicitly indicates that values were missing or not estimable for a two-arm comparison. No effect estimate, confidence interval, or p-value is reported, so there is no basis in the record for selecting or interpreting a comparative measure.

Why does precision matter? In general, an estimate from a small number of observed outcomes is uncertain. A confidence interval is one way to display that uncertainty, showing a range of effect values compatible with the data under the method used. It does not guarantee that the true effect lies within the interval. No confidence interval is reported for the primary comparison. The event counts alone cannot show how precisely an underlying group difference has been estimated.

What does randomization contribute? Random assignment is designed to make treatment groups comparable on average, including with respect to factors not measured in the study. It does not ensure that groups will be balanced in a small study, nor does it compensate for missing outcome information. The record states that allocation was randomized, but details of sequence generation, concealment, stratification, and implementation are not reported. Masking was listed as none, so the study was open-label. Whether this influenced outcome ascertainment or care use is not reported.

What analysis is documented? The registry record lists zero analyses. It does not report a statistical model, a hypothesis-testing procedure, covariate adjustment, handling of repeated events, or a prespecified estimand. An estimand is the precise treatment effect a study aims to estimate, including the population, outcome, and approach to events such as treatment changes or missing observations. These elements are not reported in the registry record. It is therefore not possible to determine whether the posted counts reflect a complete-case analysis, an intention-to-treat population, or another analysis population.

How should the planning approach be understood? The record describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the described planning approach uses total events; for other outcomes, it uses participants per arm. These are planning illustrations, not observed power and not evidence about the trial’s original design. The record does not report the trial’s own sample-size justification. No numerical planning results are stated in the information available for this analysis.

What about event rates and model assumptions? In general, binary-outcome methods require a clearly defined event and a clearly specified analysis population. Methods based on a normal approximation may be less reliable when event counts are sparse; exact methods or other approaches can sometimes be considered, depending on the design and analysis plan. This is general statistical context, not a description of a method used for this study. The registry record does not state which method, if any, was selected for the primary endpoint.

Secondary outcomes include time-to-event measures and a composite healthcare-utilization measure, which raise different analytic questions from a participant-level binary count. Time-to-event analyses can depend on how follow-up ends and how censoring is handled; a composite outcome depends on its component definitions. Those analysis details are not reported. The trial’s secondary-outcome list alone does not establish which analyses were performed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("AVAPS-AE Non-invasive Ventilation Therapy", "Standard of Care Group")
n      <- c(3, 2)
events <- c(1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  AVAPS-AE Non-invasive Ventilation Therapy  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Standard of Care Group  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes in addition to the primary outcome, and eight outcome measures overall. Testing or estimating effects across multiple outcomes can create multiplicity: in general, the more statistical comparisons made, the greater the chance that some results appear notable by chance. A prespecified strategy can address this, for example by defining a primary hypothesis or adjusting inference across a family of tests. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or which secondary outcomes were analyzed.

The record lists zero analyses. It does not report an analysis population for the primary endpoint, whether participants were analyzed in their randomized groups, or how missing outcomes were handled. These omissions matter because the stated enrollment is 18 while the posted primary outcome arm counts are three and two. The reason those figures differ is not reported in the registry record. It would be inappropriate to infer whether the difference reflects missing follow-up, exclusions, incomplete reporting, or another cause.

For a randomized trial, an intention-to-treat approach generally retains participants in their assigned groups, while other analysis populations may use different eligibility or treatment-receipt rules. This is general terminology; the registry record does not say which approach was used. It also does not describe imputation, sensitivity analyses, or whether outcome status was available for all participants. Consequently, the effects of missing data and the representativeness of the posted arm counts cannot be assessed from the record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hyperkalemia (33.3%), cardiac arrhythmia (33.3%), acute kidney infection (33.3%), fall secondary loss of consciousness (33.3%).

The serious-event fields report zero affected participants during screening, with 18 at risk. In the standard-care group, zero were affected, with four at risk. In the AVAPS-AE group, one was affected, with three at risk. Deaths are reported as zero in each of those groups. The other-adverse-event fields report zero affected participants in each group.

The record also lists Hyperkalemia, Cardiac Arrhythmia, Acute Kidney Infection, and Fall secondary loss of consciousness among the top serious-event terms, each with a reported value of 33.3%. The basis for those percentages, including how terms relate to the groups and affected participants, is not reported in the registry record. The terms should not be interpreted as showing that each occurred in every group or as establishing a relationship to the intervention.

These safety figures are descriptive counts in a small posted dataset. They do not provide a comparative safety estimate or establish whether an event was caused by treatment. The record does not report event narratives, severity gradations beyond the serious-event classification, relatedness assessments, or the full method for collecting adverse events. The screening-period figures are separate from the treatment-group figures and should not be combined into a treatment comparison.

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

The posted results describe a randomized pilot study with a primary endpoint focused on healthcare use after discharge. The recorded event counts are one participant in the AVAPS-AE group and zero in standard care, while the arm counts are three and two. These observations are the entirety of the estimable primary-outcome information reported for the comparison. They do not quantify a reliable between-group effect, because the registry record says a two-arm comparison was not estimable and reports no estimate or uncertainty interval.

The findings therefore do not establish whether AVAPS-AE changed emergent healthcare use relative to standard care. Nor do they establish that the groups were equivalent. A result that cannot be estimated is not evidence of no difference; equally, a difference in the raw counts is not enough to establish a treatment effect. This is a statistical interpretation of the posted information, not a clinical recommendation.

The study addressed a population with sleep-disordered breathing and co-morbid COPD after hospitalization, and its endpoint included more than re-hospitalization alone. That focus may be relevant to understanding what the trial set out to measure, but the registry record does not report event-level details or clarify the boundary between emergent and non-emergent use in the endpoint description. The listed secondary outcomes also span costs, quality of life, healthcare utilization, and re-hospitalization over different timeframes. Their results are not described in the information.

The record’s stated enrollment of 18 and the much smaller arm counts in the posted primary outcome do not establish why the reported outcome data cover fewer participants. No conclusion about completeness, reasons for termination, or missingness mechanism can be drawn without additional reporting. The appropriate interpretation is narrow: the registry contains sparse primary-outcome counts, no estimable two-arm analysis, and insufficient detail for a precise treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design and its posted primary results illustrate the gap between a randomized comparison and an estimable treatment effect. Randomization defines a comparative framework, but a framework alone is not a result. The primary endpoint has sparse posted counts, the record identifies the comparison as not estimable, and no comparative estimate or confidence interval is reported.

The distinction between enrollment and available outcome counts is also important. The registry states an enrollment of 18, while the posted arm-level primary outcome counts are three and two. Without an account of the analysis population and missing outcomes, readers cannot assess how those outcome data relate to the full enrolled group. This limits both precision and transparency, without revealing why the difference occurred.

The endpoint itself raises a useful measurement issue. Its title focuses on emergent healthcare, while the description mentions emergent and non-emergent utilization. Clear event definitions are essential when a participant count is used as an outcome, especially when visits can vary in urgency and type. The registry record does not explain how the definition was applied or how repeated events were treated.

Finally, this record shows why trial status and pilot designation should be kept separate from claims about results. The trial is recorded as terminated, but the reason is not reported. The available information supports a description of the study’s question, design, and posted counts; it does not support a precise comparative conclusion. That distinction is central to responsible statistical interpretation.

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 primary limitation is the absence of an estimable two-arm comparison for the endpoint. Only one event is recorded in the AVAPS-AE group and none in standard care, with arm counts of three and two. The record gives no effect estimate, confidence interval, p-value, or analysis description. The stated enrollment is 18, but the reason the outcome counts cover fewer participants is not reported in the registry record.

The registry record does not explain the termination, report the original sample-size justification, or describe the statistical analysis plan. It also does not specify the analysis population, missing-data handling, allocation implementation, or outcome ascertainment procedures. These omissions make it difficult to judge the completeness and interpretability of the posted primary data.

The endpoint wording is not fully consistent: the title describes emergent healthcare, while the description also includes non-emergent utilization. The record does not clarify the operational definition, handling of multiple visits, or whether a participant with more than one qualifying event was counted only once. Open-label conduct is recorded, but its potential influence on care-seeking or reporting cannot be evaluated from the available details.

The study was a pilot and is recorded as terminated. Neither fact alone establishes why the results are limited, but both are relevant context. The registry record does not provide outcome results for the listed secondary measures in the information available for this analysis. The safety listings also lack details about event relatedness and the denominator underlying the reported serious-event term percentages.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study to Assess the Effects of a Novel Application of Averaged Volume Assured Pressure Support Ventilation (AVAPS-AE) Therapy on Re-hospitalization in Patients With Sleep-Disordered Breathing With Co-morbid COPD — NCT02446769.
• Registry record last updated 2020-08-05; status last verified 2020-07.
• Results first posted 2019-07-10.
• 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

NCT02446769 was a randomized, multi-center, open-label, parallel-group pilot study sponsored by Philips Respironics. It compared AVAPS-AE non-invasive ventilation therapy, initiated for 60 days, with standard care according to the participant’s health care provider’s usual pathway. The study concerned hospitalized patients with sleep-disordered breathing and co-morbid COPD and was recorded as terminated.

The primary endpoint counted participants requiring emergent healthcare during 60 days post-discharge. The posted results record one participant with an event in the AVAPS-AE arm and zero in standard care, with arm counts of three and two. The registry record says that values were missing or not estimable for a two-arm comparison and reports no analyses. The stated enrollment was 18; the reason for the difference between enrollment and posted outcome counts is not reported.

The record lists six secondary outcomes and eight outcome measures overall. It does not report a comparative primary-outcome estimate, confidence interval, or p-value.