Change in Oxygen Consumption Following Inhalation Beta Agonists in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Change in Oxygen Consumption Following Inhalation Beta Agonists in Healthy Adults (NCT02802111), a randomized na study. The primary outcome is Oxygen Consumption.

2. Clinical Question

The clinical question concerns a short-term physiologic response in healthy volunteers, not treatment of airway obstruction in patients. The registry background describes the medications and the investigators’ interest in oxygen consumption and heart rate. It also notes that levalbuterol is frequently prescribed to limit cardiovascular toxicity; that statement is background rationale, not a result established by the posted summaries.

3. Trial Design

The registry describes a randomized, single-masked crossover study. Participants were assigned to which medication they received first: albuterol 5 mg followed by levalbuterol 2.5 mg, or levalbuterol 2.5 mg followed by albuterol 5 mg. Each participant received both medications. Thus, the two result groups are sequences, not independent treatment groups in which participants received only albuterol or only levalbuterol.

The later medication was administered 4 hours or greater after the first. Oxygen consumption and vital signs were measured for 1 hour after each intervention, and the primary outcome timeframe is listed as 0 to 60 minutes. The registry does not report further detail about the timing or schedule of individual measurements within that interval.

Enrollment is listed as 24. The primary outcome rows each list 24, while the narrative says participants were randomized to which medication they received first and each received both. These entries should not be added together or interpreted as separate sets of participants. The record does not explain the relationship between the enrollment figure and the row-level counts.

The study is marked completed, with phase listed as NA. The record lists Children's Hospital Los Angeles as sponsor. Its recorded start is 2015-06 and primary completion is 2017-09. Further details about masking, including who was masked, are not reported in the registry record. The record also does not describe the randomization procedure, sequence concealment, or any procedures used to address possible carryover between treatment periods.

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.

First Intervention (5 Min of Drug)

Washout (4 Hours)

Second Intervention (5 Min of Drug)

Analysis population for the primary outcome, as defined in the registry: Healthy volunteers, median age 32 years. The population is 24 individuals they are randomized to which bronchodilator they received first. Half were randomized to Albuterol and half to levalbuterol but each subject received both medication. It is a matter of which they received first. There was a four hour wash out period between the first and second medication.

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 Oxygen Consumption, measured over 0 to 60 minutes.

The primary endpoint is oxygen consumption, reported in mls/kg/min. Oxygen consumption describes the rate at which the body uses oxygen, expressed relative to body mass and time. In general, measuring a short-term physiologic response can help characterize how the body responds after an intervention. It is not, on its own, a measure of symptom relief, clinical benefit, or cardiovascular harm.

The registry specifies measurement over 0 to 60 minutes following beta agonist aerosol and identifies the summary parameter as the median, with inter-quartile range as the dispersion measure. A median describes the midpoint of observed values when ordered; the inter-quartile range generally describes the central spread. These are useful summaries when the distribution may be skewed or when a typical value and its spread are more informative than a mean and standard deviation.

The posted arm results give values of 0.28 and 0.27, with low and high values of 0.15 to 0.36 and 0.19 to 0.35, respectively. The record does not explicitly identify what those low and high values represent, and the spread field is empty. They should therefore not be described as confidence limits or as a fully reported inter-quartile range. Because results are presented by randomized sequence, they do not establish the treatment-specific change in oxygen consumption.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the study as randomized, single-masked, and crossover. These labels identify important parts of the design, but they do not specify the analysis used to produce the posted summaries. Randomization assigned treatment order. In a crossover study, participants receive both treatments in sequence, so the analysis may use the fact that measurements come from the same person. The record does not report an analysis of paired responses or give the participant-level measurements needed to reproduce one.

What does randomization of order mean?

Randomization can reduce systematic differences between the groups assigned to each sequence. Here, the randomized groups differ in which medication was received first. Since both sequence groups received both medications, a comparison of the sequence summaries is not equivalent to comparing albuterol-only participants with levalbuterol-only participants. The sequence-level medians can reflect treatment order, period effects, and other features of the sequence, as well as responses to the medications. The registry does not report whether or how these possibilities were assessed.

Why does crossover analysis need care?

In general, crossover analyses often account for within-person correlation: measurements from the same participant are related, rather than independent. They may also consider period and sequence effects. Carryover refers generally to an effect of an earlier treatment that persists into a later period. The later administration in this study was at least 4 hours after the first, but the record does not state whether this interval was selected as a washout period or whether carryover was assessed. No statistical model or adjustment for period, sequence, or carryover is reported.

How should the medians and spread be read?

The primary endpoint is identified as a median with inter-quartile range. A median is a descriptive measure of the center of observed values. In general, the inter-quartile range describes the spread of the central half of a distribution and is less influenced by extreme observations than the full range. The registry's result rows give a median-like value and low and high values, but the record does not define those low and high values; the spread field is empty. They cannot be safely relabeled as quartiles or uncertainty bounds.

A group median also differs from a median of within-person changes. In general, subtracting or otherwise contrasting group-level summaries does not recover the distribution of paired differences. The registry does not post participant-level values or a paired treatment-effect estimate. It consequently does not allow the reader to determine how consistently individual participants changed between medications.

What does an uncertainty interval usually add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified method and assumptions. Its width reflects both the variability in the data and the amount of information available. It is not interchangeable with a descriptive range or an inter-quartile range. The posted low and high values have no stated interpretation in the registry record, and no confidence interval for the treatment contrast is reported. No interval-based conclusion about the treatment difference can be drawn from these values.

Why can over-dispersion matter?

Over-dispersion is a general issue in analyses where observed variability exceeds what a model assumes. If a model fails to allow for the actual variability or correlation, its standard errors and uncertainty estimates can be misleading. This trial's posted primary summary is a median, and the registry does not report a model, a variance estimate, or an analysis of individual measurements. There is therefore no basis to say that over-dispersion was present or that a particular correction was used. This concept is relevant as a general reminder that model assumptions need to match the data, not as a finding about this study.

What can be said about the statistical plan?

The registry lists zero analyses. A detailed statistical analysis plan, treatment-effect model, handling of repeated measurements, missing-data method, and approach to multiplicity are not reported in the registry record. No sample-size justification or interim analysis is reported. The sample-size assumptions described for planning illustrations are not the trial's own design assumptions; any such illustration is a planning exercise, not observed power. The record's primary endpoint definition and summary values should not be mistaken for a complete statistical analysis.

General statistical practice distinguishes the estimate of an effect from the uncertainty around it and from a hypothesis test. This record posts descriptive sequence summaries, but no estimated contrast or inferential result for oxygen consumption. It therefore supports a description of what was recorded, not a claim about the size, precision, or statistical significance of a treatment difference.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies oxygen consumption as the primary outcome and heart rate as a secondary outcome. It reports two outcome measures, but lists zero analyses. The record does not describe a multiplicity strategy, such as how interpretation would account for examining more than one outcome or multiple measurements over time. Without that information, it is not possible to determine whether any inferential testing was planned or how it would have been interpreted.

The record does not report a statistical analysis population, exclusions, or a missing-data method. It does not state whether all randomized participants contributed every scheduled measurement, whether any observations were unavailable, or how incomplete repeated measurements were handled. The listed result counts should not be treated as proof that all scheduled measurements were complete. No participant-level accounting or analysis population definition is reported in the registry record.

In general, missing measurements can affect a result when the likelihood of missingness is related to participant characteristics or outcomes. Crossover studies also require clarity about which periods and paired observations contribute to an analysis. These are general methodological considerations; the registry does not say that missing data occurred or describe an approach for addressing them.

The registry's descriptive summaries do not resolve these questions. The record does not report a prespecified hierarchy for outcomes, adjustment for multiple comparisons, or handling of repeated time points. Accordingly, the posted information cannot establish whether multiplicity or missingness affected an inferential result.

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 adverse-event information under the two treatment-sequence labels. In each sequence group, the serious-event at-risk count is 12 and the serious events reported as affecting participants are 0. The other-event at-risk count is also 12 in each group, with 0 affected. Deaths are reported as 0 in each group, and no top serious-event terms are listed.

These safety entries are presented by sequence, not as a direct comparison of adverse events after albuterol versus after levalbuterol. The record does not explain why the at-risk counts are 12 while the primary outcome rows list 24, or how adverse events were assigned within a crossover sequence. These figures should be read as the registry's posted counts, not as evidence about comparative risk for each medication.

In general, a count of zero reported events does not demonstrate that an event is impossible or that risk is absent. Interpretation depends on how events were defined, collected, and attributed, and on the amount of observation. The registry record does not provide detailed event definitions, event-collection procedures, or medication-specific exposure-period counts. The safety figures therefore offer limited descriptive information and do not support a broad safety conclusion.

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

The posted primary outcome summaries describe oxygen consumption for the two randomized treatment sequences. The median is 0.28 for albuterol first and levalbuterol afterward, and 0.27 for levalbuterol first and albuterol afterward. The accompanying low and high values are 0.15 and 0.36 for the first sequence and 0.19 and 0.35 for the second. The registry does not define those low and high values, and it does not report a direct estimate comparing the medications.

These descriptive values do not establish equivalence, absence of a difference, or superiority of either medication. In general, a conclusion about a treatment contrast requires an estimate that matches the study design and an assessment of its uncertainty. The registry does not report the paired contrast, a confidence interval for that contrast, or a statistical test. Similar-looking sequence medians are not a substitute for those analyses.

The study's crossover structure matters: each participant received both medications, and randomization determined the first treatment. Thus, sequence-level summaries are not the same as treatment-specific summaries. An appropriate crossover analysis would need to account for the repeated measurements within participants and consider period and sequence. The registry does not report whether these features were addressed.

The population was healthy adult volunteers, and the outcome was measured over a short period after administration. The findings cannot be assumed to describe responses in patients with airway obstruction or effects on clinical outcomes. Heart rate appears as a secondary outcome, but numerical results are not reported in the registry record. The background discussion of cardiovascular toxicity is rationale, not evidence from these posted results.

The most defensible interpretation is narrow: the record contains median oxygen consumption summaries by randomized order and limited adverse-event counts by sequence. It does not provide enough analytic detail to quantify a treatment effect or its precision. These limitations apply to what can be concluded from the registry record; they do not imply that unreported analyses were or were not conducted elsewhere.

13. Why This Trial Matters Statistically

This study raises a useful statistical issue: a randomized crossover trial is not interpreted like a parallel-group trial. Participants received both medications, while randomization determined treatment order. The structure creates the possibility of comparing responses within the same participant, but the posted primary results are organized by sequence. Those summaries alone do not show the within-person treatment contrast that is central to many crossover analyses.

The record also illustrates why the definition of a reported summary matters. It identifies the median and inter-quartile range, yet the result rows provide low and high values without a separately reported spread or an explanation of those bounds. Readers need to distinguish a descriptive summary from an uncertainty interval. Without that distinction, the apparent precision of a result can be overstated.

Another important point is the separation between descriptive results and inference. The record posts values for oxygen consumption but lists zero analyses and does not report an estimated contrast, uncertainty interval, or test. A numerical result is not automatically evidence of a treatment difference, and close medians are not proof of equivalence. Transparent reporting of the analysis and its assumptions is necessary for readers to judge the strength and precision of a comparison.

Finally, the study asks a short-term physiologic question in healthy adults. That focus is statistically and clinically distinct from evaluating patient outcomes or comparative safety in clinical use. The record's sequence-level adverse-event counts and unreported heart-rate results further limit the scope of interpretation. The trial matters as an example of how design, outcome definition, and reporting detail shape what a registry result can support.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry reports oxygen consumption by randomized sequence rather than a treatment-specific contrast. Although each participant received both medications, no paired estimates or analysis accounting for the crossover structure are reported. The record does not describe period effects, sequence effects, or assessment of possible carryover. The interval between treatments was 4 hours or greater, but its analytic role is not stated.

The primary outcome is described as a median with inter-quartile range, while the results provide low and high values and no separate spread value. The record does not define the low and high values. This prevents confident interpretation of the reported dispersion and does not provide an uncertainty interval for the treatment difference. The registry also lists zero analyses, so no inferential result is available in the record.

The population is healthy adult volunteers, limiting how directly the summaries address people receiving treatment for airway obstruction. The endpoint covers 0 to 60 minutes after administration, so the record concerns a short-term physiologic response rather than longer-term outcomes. The registry lists heart rate as secondary but does not post its numerical results.

Additional details are not reported in the registry record, including the statistical analysis plan, missing-data handling, analysis population, detailed masking procedures, and rationale for the adverse-event at-risk counts. The record does not explain the relationship between enrollment and the counts in the outcome rows. These gaps limit independent assessment of precision, completeness, and the analysis strategy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Change in Oxygen Consumption Following Inhalation Beta Agonists in Healthy Adults — NCT02802111.
• Registry record last updated 2020-10-28; status last verified 2020-10.
• Results first posted 2020-10-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02802111 is a completed, randomized, single-masked crossover study of inhaled albuterol and levalbuterol in healthy adult volunteers. Enrollment is listed as 24. Participants received both medications, with randomization determining which was given first; the later treatment was administered 4 hours or greater after the first.

The primary endpoint was oxygen consumption in mls/kg/min, measured over 0 to 60 minutes. The registry identifies the summary as a median with inter-quartile range and posts values by sequence, but does not define the accompanying low and high values. Heart rate is listed as a secondary outcome without numerical results in the registry record.

The record lists zero analyses and does not report a direct treatment contrast or its uncertainty. Adverse-event counts are also organized by sequence and should not be read as a medication-specific comparison. The posted information supports a description of sequence-level summaries, but not a definitive estimate of the comparative effect of the two medications.