Effect of Nebulized Budesonide and Oral Corticosteroids on Wheezing Episode Relapse in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Nebulized Budesonide and Oral Corticosteroids on Wheezing Episode Relapse in Children (NCT00189436), a randomized phase 4 study. The primary outcome is Wheezing/Asthma/Bronchospasm Relapse Rate.

2. Clinical Question

The registry record asks whether treatment with nebulized budesonide or usual care is associated with different wheezing, asthma, or bronchospasm relapse rates among children discharged after emergency department or outpatient care. The study concerns children aged 1–8 years diagnosed with asthma, bronchospasm, or wheezing after standard care. Follow-up for the primary outcome was 3 weeks.

The comparison is between a specified nebulized treatment and a usual-care approach that could include oral steroid treatment. That means the comparator was not necessarily identical for every participant; the registry record describes usual care as determined by the doctor. The study was randomized, but open-label, so participants and study staff were not masked to assignment. The registry record lists 61 enrolled participants. The posted primary outcome summaries report 23 participants in the budesonide arm and 25 in the usual-care arm, without explaining the difference between these counts and total enrollment. The clinical question is therefore about the recorded relapse measure in the groups represented in the outcome summaries, not a detailed assessment of all possible asthma outcomes or longer-term effects.

3. Trial Design

This was a Phase 4, randomized, open-label, parallel-group study sponsored by Deborah Gentile. It is listed as completed, with enrollment of 61. The registry record lists Asthma as the condition. The study description says children discharged from emergency department or outpatient care after usual standard care were assigned to nebulized budesonide or usual care. The parallel-group structure means participants were assigned to one of the treatment groups rather than crossing between treatments. Masking was listed as none.

The treatment arm is described as nebulized budesonide 0.5 BID for 3 weeks. The usual-care arm is described as care provided by the doctor, normally albuterol with or without an oral steroid. This difference matters for interpretation: the comparison is not simply between budesonide and a single standardized drug regimen. The registry record does not report whether the usual-care components were standardized across participants, nor does it provide details of allocation concealment or the randomization procedure.

The primary endpoint timeframe was 3 weeks. Secondary outcomes were urinary cortisol levels and forced expiratory volume in 1 second (FEV1), also assessed over 3 weeks. The registry record lists 3 outcome measures but reports no posted analyses for the secondary outcomes. The primary arm summaries include 23 participants for budesonide and 25 for usual care; the safety summaries use 31 participants per arm. The record does not explain these different analysis counts or specify the analysis population for each result.

The registry record does not report a sample-size justification, a prespecified statistical analysis plan, interim analyses, or details about handling missing outcome data. The sample-size illustrations accompanying the reported secondary comparisons are based on the observed effects and are planning illustrations, not evidence about the study’s original design or its achieved power. They should not be read as showing that the trial was adequately or inadequately powered according to an unreported protocol.

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

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: 61 subjects were enrolled and 31 were randomized to nebulized budesonide and 30 to standard of care. 74% of subjects enrolled in the nebulized budesonide and 83% enrolled in the standard care group completed the study.

6. Primary Endpoint

The registry lists the primary outcome as Wheezing/Asthma/Bronchospasm Relapse Rate, measured over 3 weeks.

The primary endpoint is titled “Wheezing/Asthma/Bronchospasm Relapse Rate.” It is defined as the percentage of subjects in each group who had an unscheduled acute visit to primary care, urgent care, or an emergency department during the study period. Its timeframe is 3 weeks. This endpoint captures a clinically consequential episode that led to additional acute care, rather than every symptom or wheezing event that might have occurred at home.

Using an unscheduled visit as the endpoint can make the outcome relatively concrete: it depends on a recorded health-care encounter rather than solely on a subjective symptom score. At the same time, it measures care-seeking and service use as well as the underlying episode. An event that did not prompt a visit would not meet the registry definition. Access to care, caregiver decisions, and local practice could influence whether an episode resulted in a qualifying visit; the registry record does not describe measurement procedures intended to address those influences.

The endpoint is expressed as a percentage of subjects in each group, and the posted arm values are 8.7% for treatment with budesonide and 4.0% for usual care. These are descriptive arm summaries. The registry record does not post a comparative estimate, confidence interval, or statistical test for this primary endpoint. Without a reported comparison, the arm percentages alone do not establish the precision of the between-group difference or whether the observed pattern is compatible with a wide range of underlying effects.

The endpoint is focused on relapse during a short follow-up window. It does not, by itself, summarize lung function, hormone levels, symptom duration, or later events. Those are distinct questions, and the record lists urinary cortisol and FEV1 as secondary outcomes. The primary endpoint’s practical meaning is therefore limited to the specified unscheduled acute visits during the 3-week period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, open-label, parallel-group study. Randomization is intended to make treatment assignment independent of participants’ characteristics on average, reducing systematic differences between groups. In a small study, however, chance imbalances can still occur. The record states that allocation was randomized but does not report the sequence-generation method, allocation concealment, stratification, or other implementation details. Open-label means masking was listed as none; knowledge of assigned treatment may affect behavior or measurement, although the primary endpoint’s unscheduled-visit definition is based on an acute-care encounter.

What does a group percentage tell us?

A group percentage is a descriptive summary: it tells the reader the proportion recorded as meeting the endpoint in that arm. It does not alone quantify how much the arms differ after accounting for sampling variability. A comparative analysis would typically report an effect measure and uncertainty, such as a confidence interval, and might also report a test of a null hypothesis. For the primary relapse outcome, the registry record provides neither a comparative estimate nor a confidence interval or p-value. The reported percentages therefore should be read as arm-specific summaries, not as a complete inferential comparison.

For a binary or count-type outcome, the analysis depends on the number of participants with and without the event, the denominator used, and the chosen statistical method. Those event counts are not posted for the primary endpoint. The record also does not describe whether the analysis used a risk difference, a ratio measure, a regression model, or another approach. Since the event totals and analysis method are unavailable, an independent primary comparison cannot be recovered from the published arm percentages alone.

How should a confidence interval be read?

A confidence interval describes the precision of an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision; a wider interval indicates greater uncertainty. For a mean difference, an interval that includes zero is compatible with no difference under the corresponding statistical model, while an interval that excludes zero is less compatible with a zero mean difference at the conventional two-sided 0.05 level. This general interpretation does not establish clinical importance, eliminate bias, or address whether the analysis was planned in advance.

The secondary comparisons are labeled as recalculated and are simple unadjusted analyses from the posted means, standard deviations, and group sizes. They should not be mistaken for sponsor-reported analyses: the registry lists no reported analyses for these outcomes. The urinary cortisol comparison has a recalculated mean difference of -46.2, with a 95% confidence interval from -68.3 to -24.1 and p < 0.001. The FEV1 comparison has a recalculated mean difference of 0.5, with a 95% confidence interval from -1.088 to 2.088 and p = 0.537. Because the record does not report sponsor analyses for these outcomes, there is no sponsor analysis to take precedence over these recalculations; the estimates remain unadjusted summaries and should be interpreted cautiously.

Why does variability matter?

For continuous outcomes, a mean summarizes the central value and a standard deviation describes the spread of individual measurements around that mean. The standard error reflects uncertainty in the estimated group mean and is influenced by both variability and sample size. In a comparison of means, greater variability generally makes it harder to estimate a difference precisely. The posted secondary summaries include group means, standard deviations, and participant counts, which allow the simple unadjusted comparisons to be calculated. They do not establish whether the outcome distributions met every assumption of a conventional mean-comparison method, and the registry does not report diagnostic checks or model adjustments.

Over-dispersion is a general concern for count outcomes: it occurs when the variation in counts is greater than a simple model assumes. If present, a model that ignores it can understate uncertainty. For the primary endpoint, the registry provides percentages but no event counts or analysis model, so it is not possible to assess whether over-dispersion was relevant or how it was handled. This is a general methodological consideration, not a claim that over-dispersion occurred in this study.

What do the planning illustrations mean?

The sample-size illustrations use the observed secondary effects as a basis for hypothetical planning. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and detection of a stated fraction of the observed effect. The entries are participants per arm for the listed power targets. Such calculations can help illustrate how the required sample size changes as the target effect becomes smaller or the desired power becomes higher. They do not show the study’s original sample-size justification, which is not reported in the registry record.

These calculations are not observed power. Observed power is not a useful substitute for interpreting an estimate and its confidence interval: it is largely determined by the observed effect and its uncertainty. The planning illustrations should instead be read as conditional examples, based on effects observed in this particular dataset and assumptions that may not reflect a future study. The registry record does not report the original planning assumptions or whether the trial was designed around the primary endpoint.

What remains unknown?

The registry record does not report a statistical analysis plan, handling of missing data, analysis populations, interim analyses, or multiplicity procedures. It also does not explain the difference between the primary endpoint counts and the safety counts. These omissions prevent a full assessment of whether analyses followed prespecified methods, whether all randomized participants were included, or whether the posted secondary comparisons were selected from a broader set of analyses. These uncertainties should remain visible when interpreting otherwise precise-looking estimates.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and two secondary outcomes, but it does not report a statistical analysis plan or a procedure for handling multiple comparisons. When several outcomes are examined, each test creates an opportunity for a chance finding. If investigators interpret a collection of unadjusted tests as though only one test had been performed, the overall false-positive risk can be greater than the nominal level for an individual test. This is a general statistical concern; it does not establish that a false-positive result occurred in this study.

The recalculated secondary p-values are unadjusted. The record does not say whether these outcomes were prespecified, whether additional outcomes were analyzed, or whether any correction was applied in analyses outside the posted registry results. Because no sponsor-reported analyses are listed for the secondary endpoints, there is no documented analysis plan against which to assess selective reporting. The secondary results are best treated as exploratory, with their estimates and confidence intervals considered alongside their limited sample sizes and the absence of reported multiplicity procedures.

Missing-data handling is not reported in the registry record. The primary summaries list 23 participants in the budesonide arm and 25 in usual care, whereas safety summaries list 31 in each arm. Total enrollment is listed as 61. These counts may reflect different analysis sets or available measurements, but the reason is not reported and should not be inferred. The record does not state how many participants were randomized to each group, whether any withdrew, whether all had endpoint ascertainment, or how unavailable measurements were treated.

The analysis population is likewise not reported in the registry record. It is not possible to determine from the posted information whether the primary or secondary analyses followed an intention-to-treat approach, included only participants with observed outcomes, or used another defined population. These distinctions matter because excluding participants after randomization can affect the comparability created by random assignment. Without a documented population definition and missing-data approach, the scope of the estimates cannot be fully assessed.

The registry record also does not report interim analyses. This absence of reporting is not evidence that interim monitoring did or did not occur. Details of prespecified stopping rules, if any, are also not reported in the registry record. Overall, multiplicity, missingness, and analysis-population information are too limited to determine how these issues were addressed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The safety summaries report zero serious adverse events among 31 participants at risk in the treatment-with-budesonide group and zero among 30 participants at risk in the usual-care group. They also report zero other adverse events in both groups, with 31 and 30 participants at risk, respectively. These figures describe what was recorded in the registry’s safety summaries; they do not establish that no adverse events could occur or that the groups have equivalent safety.

A zero count is especially difficult to interpret as evidence of similarity when the number of participants observed is limited. The registry record does not provide confidence intervals for these event counts, details about the duration or completeness of safety surveillance, or definitions for the adverse-event categories beyond their labels. It also does not report a deaths figure in the posted safety summaries. No serious adverse event terms are listed.

The safety population counts differ from the primary outcome counts, and the registry record does not explain why. Therefore, the safety figures should not be assumed to use the same participants or analysis population as the relapse outcome. They are descriptive registry summaries, not a comparative statistical test. They provide no basis on their own for concluding that the treatments are equally safe or for making an individual treatment decision.

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

The registry record establishes that a randomized, open-label comparison was conducted and reports arm-specific primary relapse percentages over a 3-week follow-up. The reported values are 8.7% for treatment with budesonide and 4.0% for usual care. These figures describe the observed summaries, but the record does not include the primary comparative estimate or its uncertainty. As a result, the size and precision of the between-group difference are not established by the posted primary results.

The secondary results offer distinct, unadjusted statistical comparisons for urinary cortisol and FEV1. They should not be treated as replacements for the missing primary comparison, nor do they establish why the primary arm percentages differ. Their interpretation is limited by the absence of reported analyses, multiplicity procedures, missing-data methods, and analysis-population definitions. A statistically notable secondary comparison does not by itself answer the primary clinical question.

The findings also do not establish that the observed results would apply to every child with wheezing or asthma. The study description focuses on children aged 1–8 years discharged from emergency or outpatient care after standard care. The comparator is usual care as determined by the doctor, normally albuterol with or without an oral steroid. The registry record does not give enough detail to assess variation in care, recruitment, or outcome ascertainment beyond those descriptions.

These results do not demonstrate that either treatment works or does not work. They do not show that the groups are equivalent, and a lack of a reported primary test is not evidence of no difference. Similarly, the zero recorded adverse-event counts do not prove the absence of risk. Statistical uncertainty, study size, the brief follow-up, and incomplete reporting all constrain what can be concluded.

The most defensible reading is narrow: the registry reports the primary arm percentages and several secondary summaries, but does not report the analysis needed for a precise primary comparison. The observed summaries can motivate further examination, while the information in the record is insufficient to turn them into a firm conclusion about comparative efficacy, safety, or longer-term outcomes.

13. Why This Trial Matters Statistically

This study is statistically instructive because the primary endpoint is reported as group percentages without a comparative estimate, confidence interval, or test. A descriptive result can appear straightforward while leaving the central inferential question unresolved. Readers need to distinguish a pair of arm summaries from an estimate of the difference between groups and from an assessment of uncertainty around that difference.

The record also illustrates why denominators matter. Enrollment is listed as 61, the primary summaries use 23 and 25 participants, and the safety summaries use 31 and 30 participants. Those counts cannot be reconciled from the registry information. When analysis populations are not explained, even basic questions about who contributed to each result remain open. This is not a mathematical technicality: the meaning of an estimate depends on which participants and outcomes it represents.

Another statistical lesson is that secondary outcomes should be interpreted in relation to the primary question and the possibility of multiple testing. A result can be statistically notable on one secondary measure while another is not, yet neither necessarily answers the main clinical question. Without a reported analysis plan or multiplicity procedure, unadjusted secondary comparisons have a more exploratory status.

The posted sample-size illustrations also show the distinction between planning calculations and trial design evidence. Calculations using observed effects can describe hypothetical future study sizes under stated assumptions. They do not reveal the original rationale for enrollment, and they are not observed power. The registry record does not report the original sample-size justification.

These issues are relevant across clinical research: effect estimates, confidence intervals, denominators, prespecified outcomes, and analysis populations are all part of interpreting evidence. Missing details should remain uncertainties rather than being filled in by assumptions. In this record, the absence of a primary comparative analysis is central to the limits of interpretation.

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 limitations are specific to the information reported for this trial. First, the primary endpoint is presented as arm-specific percentages, without event counts, a between-group effect estimate, a confidence interval, or a p-value. This prevents a precise evaluation of the primary comparison. The outcome definition is based on an unscheduled acute visit, so it captures episodes resulting in care-seeking rather than all possible wheezing or asthma events.

Second, the reported participant counts differ across the record. Enrollment is 61, the primary outcome summaries include 23 participants for budesonide and 25 for usual care, and the safety summaries include 31 participants per arm. The reason for those differences is not reported in the registry record. Withdrawal, missing measurements, and the analysis populations are not described, so it is not possible to determine how representative each set of summaries is of all randomized participants.

Third, the study is open-label, with masking listed as none. The registry record does not describe procedures to limit potential effects of treatment knowledge on behavior, care-seeking, or assessment. The usual-care arm is described as albuterol with or without an oral steroid, with care provided by the doctor. The degree of variation in this comparator is not reported.

Fourth, the follow-up for the primary endpoint and secondary outcomes is 3 weeks. The posted results therefore do not describe longer-term relapse or outcomes outside that timeframe. The secondary comparisons are unadjusted recalculations, and the registry lists no reported analyses for them. Prespecification, multiplicity handling, and missing-data methods are not reported. These limitations do not show that the results are biased, but they restrict the strength and scope of conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Nebulized Budesonide and Oral Corticosteroids on Wheezing Episode Relapse in Children — NCT00189436.
• Registry record last updated 2021-02-01; status last verified 2021-01.
• Results first posted 2014-08-04.
• 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 completed Phase 4, randomized, open-label, parallel-group study of nebulized budesonide versus usual care for children aged 1–8 years discharged after care for asthma, bronchospasm, or wheezing. Total enrollment is listed as 61. The primary outcome was the percentage of subjects with an unscheduled acute visit during 3 weeks. The arm summaries are 8.7% for budesonide and 4.0% for usual care, but no primary comparative analysis is posted.

Two secondary outcomes are listed: urinary cortisol and FEV1. Their posted group summaries support unadjusted recalculations, but the registry lists no reported analyses for them. Safety summaries report zero serious and zero other adverse events in both groups, with different participant counts from the primary summaries. The record does not explain the analysis counts or report a statistical analysis plan, sample-size justification, missing-data methods, analysis populations, interim analyses, or multiplicity procedures.