Comparison of Breath-Enhanced and T-Piece Nebulizers in Children With Acute Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Breath-Enhanced and T-Piece Nebulizers in Children With Acute Asthma (NCT02566902), a randomized na study. The primary outcome is Change in FEV1 (% Predicted).

2. Clinical Question

The study is described as a blinded observer randomized controlled trial. Its central statistical question is whether the observed difference in average lung-function change is compatible with chance variation under a model of no group difference. The registry reports the group means, confidence intervals, and a two-sided test result. Those measures address the size and precision of the observed changes and the evidence from the specified test, but they do not by themselves establish whether a difference is important to patients.

The record also identifies outcomes involving clinical scores, admission, emergency department length of stay, medication side effects, albuterol quantity, respiratory rate, and heart rate. Those outcomes broaden the study questions beyond spirometry, but their availability and statistical interpretation depend on the results actually reported for each measure.

3. Trial Design

This was a randomized, parallel-group trial with single masking. The intervention groups were T-piece Nebulizer and Breath-Enhanced Nebulizer. The registry describes the study as a blinded observer randomized controlled trial, but does not specify which parties were masked or how masking was maintained. The phase is listed as NA.

The enrollment was 118, and the registry status is completed. The record gives a study start of 2015-10 and a primary completion date of 2017-06-30. Both groups received a one-time 5mg nebulized albuterol treatment through their assigned device. Pre-treatment spirometry was assessed at enrollment, and post-treatment spirometry was assessed 10 minutes after albuterol administration. The reported primary change is post-treatment FEV1 minus pre-treatment FEV1.

The primary outcome summaries include 55.0 participants in the T-piece group and 52.0 in the breath-enhanced group. The registry notes that eight subjects could not complete post-treatment spirometry: three in the T-piece group and five in the breath-enhanced group. The record does not report the method used to handle these missing measurements or a detailed analysis-population definition.

Additional listed outcomes include changes in PAS and PASS scores, inpatient admission, emergency department length of stay, medication side effects, total albuterol quantity, respiratory rate, and heart rate. The record reports safety counts separately from the primary spirometry summaries. It does not report a protocol, the randomization sequence or concealment method, a sample-size justification for the trial itself, or a detailed statistical analysis plan. Those omissions limit what can be concluded about design choices beyond the randomized, parallel-group, single-masked structure described in the registry.

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: Eight subjects unable to complete post-treatment spirometry (three in T-piece group, five in breath-enhanced group)

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 FEV1 (% Predicted), measured over 10 minutes.

The primary endpoint is change in FEV1 expressed as a percentage of predicted FEV1. FEV1 is a spirometric measure of how much air a person exhales during the first second of a forced breath; expressing it as percent predicted relates the measurement to a reference expectation. The endpoint is a change score: the post-treatment measurement minus the pre-treatment measurement. A positive mean change therefore represents an increase from baseline on this scale.

Measurements were taken at baseline, before albuterol therapy, and 10 minutes after the one-time nebulized albuterol treatment. Change from baseline is used to describe within-participant movement over the measurement interval and to compare the average movement between device groups. Because both groups received albuterol, the comparison concerns the differences observed between the two nebulizer-device groups, not the effect of albuterol versus no albuterol.

The registry reports mean change and 95% confidence intervals for each group. The T-piece group mean was 13.8, with a 95% confidence interval from 10.5 to 17.2. The breath-enhanced group mean was 9.1, with a 95% confidence interval from 6.1 to 12.1. These intervals describe uncertainty around each group mean, not directly around the difference between groups. The registry’s reported two-sided t-test addresses that between-group comparison. The clinical importance threshold for a change in this measure is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s FEV1 change is a numerical measurement, and the registry summarizes the group results as means. A mean is the arithmetic average of the observed values. For this endpoint, the score is calculated as post-treatment FEV1 minus pre-treatment FEV1. The group mean therefore describes average change, not the experience of every participant.

What do the confidence intervals describe?

In general, a confidence interval communicates uncertainty about an estimated quantity under the method used to construct it. A narrower interval indicates greater precision for that estimate, while a wider interval indicates more uncertainty. The posted intervals are for each arm’s mean change: 10.5 to 17.2 for the T-piece group and 6.1 to 12.1 for the breath-enhanced group. They are not the confidence interval for the difference between arms. The registry does not report a primary between-group confidence interval, so the precision of that contrast is not directly quantified in the posted primary results.

What does the reported test assess?

The sponsor reports a two-sided t-test for the primary comparison. In general, a two-sided test evaluates departures in either direction from a null model of no group difference. A t-test compares group means while accounting for the variability in the observations and the amount of information available. Its result depends on assumptions about the data and analysis, including how the observations are treated and how their variability is represented. The detailed assumptions and implementation are not reported in the registry record. The reported p-value is 0.04. A p-value is not an effect-size estimate, a measure of clinical importance, or the probability that the null model is true.

Why do missing measurements matter?

The registry states that eight subjects could not complete post-treatment spirometry, with three in the T-piece group and five in the breath-enhanced group. Because the endpoint is calculated from pre- and post-treatment measurements, a missing post-treatment value prevents the usual change score from being observed for that participant. In general, missing outcomes can affect both the analysis sample and the estimated group comparison, particularly if missingness is related to participant characteristics or outcome values. The registry does not report an imputation procedure, sensitivity analysis, or reasons for the incomplete tests. The primary summaries include 55.0 and 52.0 participants, and the record does not describe in detail how these analysis counts were selected.

How should binary outcomes be read?

For an outcome such as inpatient admission or medication side effects, the registry reports participant counts in the two groups and a sponsor-reported test. A count states how many participants had the outcome; it should be interpreted alongside the number assessed. A recalculated risk difference is an unadjusted comparison of the observed proportions, with a confidence interval expressing uncertainty under its method. The interval can include values in either direction when the data do not sharply distinguish a difference. Such calculations do not replace the sponsor’s analysis and do not adjust for other outcomes or covariates.

In general, binary outcomes can be imprecisely estimated when events are uncommon or sample sizes are limited. A wide interval indicates that the observed counts are compatible with a broad range of underlying group differences. A non-small p-value does not establish that the groups are equivalent; demonstrating equivalence requires a prespecified margin and an analysis designed for that question. The registry record does not report an equivalence margin.

What do planning illustrations mean?

The sample-size illustrations use the observed effect as a planning reference, with assumptions of a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. They show hypothetical participants per arm for 80% or 90% power when planning for 100%, 75%, or 50% of the observed effect. These are planning illustrations, not the trial’s own design justification, and not observed power. They are sensitive to the observed effect: an effect chosen to be smaller than the observed one leads to a larger planning requirement under the stated approach. The illustrations do not establish that the trial was adequately or inadequately powered, because the trial’s own sample-size assumptions and justification are not reported in the registry record.

In general, over-dispersion means that observed variability is greater than assumed by a simple statistical model. If present and not handled, it can make estimated uncertainty too small. The registry record does not report an over-dispersion assessment for the outcomes, and there is no basis to claim that it occurred in this trial. More broadly, the test result should be read with the endpoint definition, analysis sample, missingness, and uncertainty summaries rather than as a stand-alone verdict.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a two-sided t-test with p = 0.04. It also reports arm-level mean changes and 95% confidence intervals, but no numerical estimate or confidence interval for the primary difference between arms. The arm-level summaries and the test result answer related but distinct questions: the means describe change within each group, while the test assesses a between-group contrast.

The recalculated comparisons presented for selected secondary outcomes are simple unadjusted calculations from the posted summary statistics. They are not substitutes for the sponsor’s prespecified or original analysis. No separate recalculated primary contrast is reported in the record, so a numerical recalculation cannot be used to independently check the sponsor’s primary p-value from the primary information posted. The record does not flag a discrepancy requiring the sponsor’s result to be set aside.

Accordingly, the primary statistical interpretation should retain the sponsor’s reported test as the analysis result, while noting the limited reporting of the contrast estimate and its precision. For secondary outcomes, recalculated estimates can help describe the observed counts and uncertainty, but they remain unadjusted and should not be treated as a replacement for a fuller analysis plan. The registry does not report that plan in sufficient detail to determine whether the posted tests were selected in advance or how multiple outcomes were handled.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies eight secondary outcomes in addition to the primary FEV1 change outcome. These cover clinical scores, admission, emergency department length of stay, medication side effects, albuterol quantity, respiratory rate, and heart rate. The registry does not report whether outcomes were placed in a prespecified hierarchy, whether a multiplicity adjustment was used, or whether any outcome was designated exploratory. With multiple outcomes, unadjusted tests can produce apparently notable results by chance; this general concern makes isolated secondary p-values less conclusive.

The primary outcome has missing post-treatment spirometry for eight subjects: three in the T-piece group and five in the breath-enhanced group. The primary summaries include 55.0 participants for T-piece and 52.0 for breath-enhanced. The record does not report the missing-data mechanism, an imputation method, a sensitivity analysis, or whether the analysis followed intention-to-treat or another population definition. It is therefore not possible to determine from the registry alone how the missing measurements were handled beyond the posted summary counts.

The total enrollment is 118. The safety counts are reported for 58 participants in the T-piece group and 57 in the breath-enhanced group, while the primary spirometry summaries include fewer participants. The record does not supply a participant-flow account that reconciles all analysis populations or explains every difference in available outcome counts. Such information would help readers assess whether outcome availability differed across groups or measures.

The registry does not report a protocol-level sample-size justification, the trial’s planned significance level, interim analyses, or a detailed statistical analysis plan. The planning illustrations associated with selected secondary outcomes are not the trial’s original sample-size rationale. Without the planned analysis details, the record cannot establish which analyses were primary to the investigators’ decision process, how missing data were intended to be addressed, or how the family of outcomes was to be interpreted. These are reporting limitations, not evidence that a particular analysis choice was made incorrectly.

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 non-serious adverse event terms

The registry reports zero serious adverse events in each group and zero deaths in each group. The serious-event risk counts are 58 in the T-piece group and 57 in the breath-enhanced group. It also reports five other adverse events in each group. These are counts recorded during the study; they do not by themselves quantify the full range of possible risks or establish that the devices have identical safety profiles.

Zero reported serious events should be read as no serious events recorded among the participants represented in the registry safety counts, not as proof that serious events cannot occur. In general, rare outcomes are difficult to characterize precisely in a study of this size. The registry does not list serious adverse-event terms, and it does not provide detailed descriptions of the five other events in each group or a further account of their clinical nature. The timeframe and ascertainment details for the safety summaries are not reported in the registry record.

These safety counts are distinct from the medication side-effect outcome, which is listed separately among the secondary outcomes. The posted safety record is a concise event count, not a comprehensive assessment of risk over longer follow-up.

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

The primary results describe short-term mean FEV1 change after a one-time nebulized albuterol treatment delivered through one of two devices. The registry reports positive average changes in both groups and a two-sided t-test p-value of 0.04 for the comparison. This is evidence from the reported statistical test, not a direct measure of how large or important the group difference is for an individual child.

The result does not show how many participants experienced a clinically important change, because participant-level results and a clinical-importance threshold are not reported. It does not describe outcomes beyond the 10-minute spirometry assessment, and it does not compare albuterol with no albuterol. Both groups received albuterol; the randomized comparison is between the delivery-device groups in that treatment context.

The result also does not establish equivalence or lack of equivalence. A failure to find a difference would not by itself prove equivalence, and the reported p-value does not answer that question. The registry does not report an equivalence margin or an equivalence design. Nor does a p-value alone establish causation beyond the randomized group comparison, resolve the consequences of missing post-treatment spirometry, or account for the other outcomes examined.

The posted arm-level confidence intervals quantify uncertainty around each group mean, but no primary confidence interval for the between-group difference is reported. As a result, readers have less direct information about the precision and range of plausible values for the contrast than they would with a contrast estimate and its interval. The unreported clinical threshold also prevents a direct judgment about practical importance from the statistical summaries alone.

The most defensible interpretation is limited to the registry’s reported outcome, timepoint, and analysis: the groups had different observed average changes, and the sponsor’s two-sided test returned p = 0.04. The record does not provide enough detail to translate this into a broader claim about longer-term effects, patient experience, or comparative treatment value.

14. Why This Trial Matters Statistically

This trial is statistically informative because it compares two delivery devices under a shared treatment setup and measures change from baseline in a continuous outcome. The randomized parallel-group structure makes a group comparison relevant to the device question, while the paired pre- and post-treatment measurements define a short-term change score rather than relying only on a post-treatment value.

The record also illustrates why an inferential result needs more than a p-value. The primary test result is reported, but the between-group estimate and its confidence interval are not. The group means and their intervals give useful context, yet they do not directly show how precisely the contrast was estimated. This distinction matters when readers want to assess both the direction and magnitude of a group difference.

Missing spirometry is another important statistical feature. Eight participants could not complete the post-treatment measurement, and the registry does not describe the missing-data approach or a sensitivity analysis. Because the primary endpoint depends on the post-treatment test, transparent reporting of missingness and analysis populations is essential for judging how robust the estimate may be.

The range of secondary outcomes makes multiplicity relevant. Several outcomes address different aspects of the acute-care setting, but the registry does not report a strategy for interpreting multiple tests together. Unadjusted secondary findings should therefore be treated cautiously, especially when some listed measures lack a reported two-arm estimate.

Finally, the sample-size illustrations are planning exercises based on observed effects and stated assumptions, not evidence of observed power or proof that the trial’s design was adequate. The record does not report the original sample-size rationale. Taken together, these features make the trial a useful example of how randomization, endpoint definition, missing outcomes, confidence intervals, and multiplicity all shape the interpretation of a clinical comparison.

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.

Several limitations arise from the information reported for this particular trial. The primary comparison is represented by arm-level means and confidence intervals plus a two-sided test result, but the registry does not report the numerical between-group estimate or its confidence interval. That makes the contrast’s magnitude and precision less direct to assess than the individual group summaries.

Post-treatment spirometry was unavailable for eight subjects, with three in the T-piece group and five in the breath-enhanced group. The registry does not report why those measurements could not be completed, how missing outcomes were handled, or whether analyses tested sensitivity to different assumptions. The primary analysis population is not defined in detail, and participant flow across outcome measures is not fully explained.

The record describes single masking but does not identify who was masked or how masking was maintained. It does not report allocation concealment, adherence details, or the complete administration details for the device treatments. The exact eligibility criteria and age range are also not reported in the registry record. These omissions restrict assessment of trial conduct and the applicability of the results.

The primary endpoint is measured 10 minutes after treatment, so the reported comparison is limited to an early spirometric response. The registry does not report a clinical-importance threshold for FEV1 change. It also does not report a detailed statistical analysis plan, an original trial sample-size justification, or how multiplicity across secondary outcomes was handled. Some listed outcomes do not have a reported two-arm numeric comparison, and the safety record gives event counts without detailed descriptions. These limitations do not erase the posted results, but they narrow the conclusions that can be drawn from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comparison of Breath-Enhanced and T-Piece Nebulizers in Children With Acute Asthma — NCT02566902.
• Registry record last updated 2021-05-06; status last verified 2021-04.
• Results first posted 2021-05-06.
• 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

The registry describes a completed randomized, parallel-group, single-masked trial in children with acute asthma, comparing T-piece and breath-enhanced nebulizers for delivery of a one-time 5mg nebulized albuterol treatment. Enrollment was 118. The primary endpoint was change in FEV1 (% predicted) 10 minutes after treatment. Mean change was 13.8 in the T-piece group and 9.1 in the breath-enhanced group; the sponsor reported a two-sided t-test p-value of 0.04.

Eight subjects could not complete post-treatment spirometry. The record also lists multiple secondary outcomes, but numerical two-group results are not available for every listed measure. Serious adverse events and deaths were reported as zero in both groups. The registry does not report a detailed analysis plan, the trial’s own sample-size justification, a primary between-group confidence interval, or a missing-data analysis.