Aerosolized Albuterol Use in Severe BPD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aerosolized Albuterol Use in Severe BPD (NCT02766673), a randomized na study. The primary outcome is Change in Expiratory Flow Between Pre and Post-medication Dosing.

2. Clinical Question

The clinical question arises from uncertainty about aerosolized albuterol dosing in infants with BPD. The registry summary notes that several dose schedules were in use and that there was no standard recommended dose for this population. It also describes a difference between common weight-based medication dosing and aerosol-science recommendations not to titrate aerosol doses by weight. The trial was intended to compare a dose recommended in aerosolization literature with common dosing practice at Children's Hospital of Philadelphia and with placebo.

The primary outcome was a short-term physiological measure, not a measure of longer-term lung health or clinical course. A secondary outcome recorded percent change in heart rate between pre- and post-medication dosing. Thus, the posted results address immediate changes in selected measurements during the treatment period. They do not by themselves establish whether any observed change is clinically important, persists beyond the reported timeframe, or translates into a difference in broader health outcomes.

3. Trial Design

The registry record describes a randomized, triple-masked, crossover trial, marked completed. Enrollment was 24. The listed start was 2016-08 and primary completion was 2018-06. The sponsor was Children's Hospital of Philadelphia. The phase is recorded as NA.

A crossover design means that participants receive more than one treatment condition over the course of the trial, so each participant can contribute measurements under different conditions. That structure can make within-participant comparisons informative because measurements from the same infant may be related. However, the registry record does not report the treatment sequence, any washout period, or details of how the analysis accounted for repeated observations and within-infant correlation. Those details should not be inferred from the design label alone.

The three treatment conditions were full-dose albuterol, half-dose albuterol, and sterile saline. Each was administered via nebulizer and mechanical ventilator. The primary outcome description says EF75 was measured before a treatment and again 15-30 min after each treatment phase. The stated timeframe was every 4 hours in each treatment group, up to 24 hours. The description says each subject had the potential for 6 paired observations (12 measures) per treatment group. It also notes that 2 subjects did not complete all 3 treatment groups and that some measurements were missed.

The posted outcome summaries list 23 observations or participants in each treatment group, but the record does not provide a complete account of the analysis population or the handling of missing measurements. It also does not report the original sample-size justification, the randomization sequence, or the masking procedures in operational detail. The registry lists no reported analyses for the outcomes, so the comparisons discussed in the posted results should not be mistaken for a fully described sponsor analysis.

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.

Before assignment: The original study sample size called for 25 subjects. The block randomization scheme of 6 treatment sequences within 1 randomization block. Therefore we recruited 24 patients to complete 4 randomization block. the 25th patient would have started a new randomization block and make one treatment sequence more common that the others.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Each subject had the potential for 6 paired observations (12 measures) per treatment group (comparison of measure before and after each dose of the study drug). 2 subjects did not complete all 3 treatment groups. Some measurements were missed leaving less than the total potential number of observations.

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 Expiratory Flow Between Pre and Post-medication Dosing, measured over every 4 hours in each treatment group, up to 24 hours.

The primary endpoint is change in expiratory flow between pre- and post-medication dosing. The measure is expiratory flow at 75% of vital capacity, called EF75 in the outcome description and reported in L/min. It is obtained from a ventilator flow-volume loop: the description explains that the clinician selects a mechanical breath, determines the tidal volume, identifies the point corresponding to 75% of exhalation, and records the flow at that point.

Comparing a measurement before treatment with one after treatment gives a short-term within-treatment change. Repeating that paired measurement across the treatment conditions provides a way to describe whether the recorded change differs among full-dose albuterol, half-dose albuterol, and saline. The endpoint is relevant to the stated question because it is a direct measurement of expiratory flow in mechanically ventilated infants with BPD, rather than a symptom report or a longer-term clinical outcome.

As a general statistical point, a physiological measurement can be useful for detecting short-term changes while still having limitations as a surrogate for outcomes that matter over a longer period. The registry record does not state a threshold for a clinically meaningful EF75 change. It also does not report how the outcome's direction was coded, so interpretation should focus on the posted values and comparisons rather than assigning a clinical meaning to a positive or negative value beyond the record's definition.

7. Results Posted in the Registry

• Half Dose Albuterol Sulfate: mean 0.70 versus 0.38 on control; difference 0.32 (95% CI -1.04 to 1.68), standardized effect d = 0.14; z-test p = 0.644.
• Sterile Saline: mean 0.45 versus 0.38 on control; difference 0.07 (95% CI -1.32 to 1.46), standardized effect d = 0.03; z-test p = 0.921.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Half Dose Albuterol Sulfate: mean 0.03 versus 0.07 on control; difference -0.04 (95% CI -0.12 to 0.03), standardized effect d = -0.35; z-test p = 0.242.
  • Sterile Saline: mean 0.01 versus 0.07 on control; difference -0.07 (95% CI -0.13 to -0.00), standardized effect d = -0.60; z-test p = 0.043.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Half Dose Albuterol Sulfate and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Sterile Saline than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcome concerns percent change in heart rate between pre- and post-medication dosing. Its posted group means follow a descending pattern from full-dose albuterol to half-dose albuterol to saline. The unadjusted contrast of saline with full dose is the only posted secondary comparison whose confidence interval excludes zero and whose unadjusted p-value is below 0.05; the half-dose contrast has an interval that includes zero. These are descriptions of the posted secondary data, not proof of a treatment effect.

The primary endpoint and the secondary endpoint measure different physiological features over the same general treatment period. The primary result compares changes in expiratory flow; the secondary result records percent change in heart rate. The secondary finding does not resolve the uncertainty around the primary comparisons, and it should not be treated as a substitute for them. The registry does not report a prespecified hierarchy that would make the secondary result confirmatory if the primary outcome were inconclusive.

Unadjusted secondary results carry less weight when more than one endpoint or comparison is examined. General statistical principle: with repeated opportunities to find a small p-value, the chance of at least one apparently notable result can increase, even when no underlying effect exists. An adjustment or a prespecified testing sequence can address that issue, but no multiplicity strategy is reported in the registry record. The secondary p-value should therefore be interpreted as exploratory, particularly because the record lists no sponsor-reported analyses.

The secondary outcome summaries are also subject to the same design and reporting limitations as the primary outcome. The registry describes repeated pre- and post-treatment measurements, missing measurements, and incomplete treatment groups, but does not specify the secondary analysis population or its missing-data handling. The posted means and unadjusted contrasts are informative as a pattern in the recorded data, but they do not establish a durable or clinically important heart-rate response.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing

9. Statistical Interpretation

10. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized by means and standard deviations. The posted group summaries and contrasts are useful for describing the observed data, but they do not replace a complete analysis plan or an analysis that reflects the crossover structure. The record lists no reported analyses for the primary outcome. The contrasts discussed in the results are simple unadjusted re-calculations from the posted summary statistics.

What does a mean difference describe?

A mean difference compares the average recorded outcome in one treatment condition with the average in a reference condition. In the posted primary comparisons, full-dose albuterol is the reference; the estimates compare half-dose albuterol and sterile saline with full dose. A mean difference near zero indicates that the two posted group means are close on the outcome's measurement scale. A mean difference away from zero describes a separation in the posted means, but the estimate alone does not show how precisely that separation is known or whether it is clinically meaningful.

The primary outcome is a change measure based on pre- and post-treatment observations. In a crossover trial, observations can be paired within an infant and repeated across treatments. A suitable analysis may need to account for this dependence. General statistical principle: measurements from the same individual often share characteristics, so treating them as unrelated can give an incomplete account of uncertainty. The registry record does not report whether the sponsor's intended analysis used paired changes, a repeated-measures model, or another approach. The re-calculated contrasts use posted group summaries and cannot recover the within-infant relationships that are absent from those summaries.

What does the standard deviation tell the reader?

A standard deviation describes the spread of individual measurements around a group mean. It is not the uncertainty in the mean itself, and it does not give the range of all individual values. The primary outcome standard deviations were 2.3 for full-dose albuterol, 2.4 for half-dose albuterol, and 2.5 for saline. These spreads are notably larger than the differences between the posted means, which helps explain why the group-level contrasts are imprecise. This is a descriptive comparison; it is not a separate test of treatment effects.

General statistical principle: when individual observations vary substantially, the mean difference can be estimated less precisely unless the data contain enough information to offset that variability. In crossover data, the correlation between measurements within an individual can also influence precision. Marginal means and standard deviations do not communicate that correlation. Since it is not reported in the registry record, the uncertainty calculated from the posted summaries cannot fully represent all aspects of the design.

How should confidence intervals and p-values be read?

A confidence interval describes a range of estimates that are reasonably compatible with the data and the calculation's assumptions. It conveys both the direction and the precision of an estimate. An interval that includes zero does not demonstrate that the treatments are the same; it indicates that the data and method do not sharply distinguish the estimate from zero at the interval's stated confidence level. Conversely, an interval excluding zero does not, by itself, establish clinical importance or protect against issues such as multiple comparisons or a mismatch between the calculation and the design.

A p-value describes how surprising data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor is it the probability that a result occurred by chance. The posted p-values are unadjusted. The registry does not state that they account for the number of outcomes, treatment comparisons, or repeated measurements.

What does masking and randomization contribute?

Random allocation can reduce systematic differences in how treatment conditions are assigned, while masking can reduce the influence of expectations on treatment delivery, assessment, or interpretation. The registry records the trial as randomized and triple-masked. It does not describe which trial roles were masked, how masking was maintained, or how crossover sequences were assigned. These design labels are informative but do not establish that every potential source of bias was prevented.

A crossover design has a further feature: a participant can act as a reference for their own measurements across treatment conditions. General statistical principle: this can reduce the influence of stable differences between participants, but the analysis must still consider period effects, treatment order, possible carryover, and repeated-measure correlation when relevant. The registry record does not report how these features were handled. The treatment order and any washout procedures are not reported in the registry record.

Why does the missingness description matter?

The primary outcome description states that 2 subjects did not complete all 3 treatment groups and that some measurements were missed. It also describes a potential for 6 paired observations (12 measures) per treatment group. The record does not specify the number of missing measurements, the reasons for missingness, or the method used to include incomplete observations. General statistical principle: missing data can affect estimates if the reason a measurement is absent is related to the outcome or treatment. Without details about the pattern and handling of missingness, readers cannot assess that possibility.

In short, the descriptive summaries offer a transparent view of the posted means, variability, and simple contrasts. They are not a substitute for a fully specified crossover analysis. The analysis population, model, covariance structure, treatment-period handling, missing-data strategy, and any adjustment for multiple comparisons are not reported in the registry record.

11. Confidence Intervals and Precision

Precision is best judged from the confidence intervals alongside the estimated mean differences. For half-dose albuterol compared with full-dose albuterol, the primary mean difference was 0.32 L/min, with a 95% confidence interval from -1.039 to 1.679. For sterile saline compared with full-dose albuterol, the mean difference was 0.07 L/min, with a 95% confidence interval from -1.318 to 1.458. Each interval includes zero and extends to values on either side of zero. The estimates therefore do not locate the underlying contrast narrowly.

The breadth of an interval reflects uncertainty under the method used to calculate it. In general, uncertainty depends on the amount of information, the spread of measurements, and the analysis assumptions. The posted primary group standard deviations were 2.3, 2.4, and 2.5, while the group summaries list 23 in each treatment condition. The trial was a crossover study, but the recalculations use posted summary statistics; the within-participant correlation and other design-specific details are not reported. The intervals should therefore be interpreted as unadjusted summary-based estimates, not as evidence that all sources of crossover uncertainty have been modeled.

An interval containing zero is not proof of no difference, and a wide interval does not show that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether uncertainty lies within that margin; such a margin is not reported in the registry record. Nor does a statistically significant result automatically imply a clinically meaningful difference. The registry record does not report a threshold for clinically meaningful change in EF75.

The secondary heart-rate comparison of saline with full-dose albuterol had a narrower interval that excluded zero, but it remains an unadjusted secondary result. Its precision should be considered together with multiplicity and the lack of a reported analysis plan. In general, confidence intervals are most useful when the underlying analysis matches the design and the outcome's missingness and repeated-measure structure are adequately addressed.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial's original design justification. The figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: the outcome is continuous, and the planning display gives participants per arm. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect equal to the stated fraction of the observed effect.

The 80% power column describes a hypothetical design that would have an 80% chance of detecting the specified effect under the planning assumptions if that effect were the true one. The 90% column expresses the same idea with a higher chance of detecting that effect, which generally requires more participants. These figures are planning quantities, not a claim about the probability that the completed trial detected an effect. This is not observed power.

Each row scales the target effect relative to the observed estimate: one uses the full observed effect, while the other rows plan for 75% or 50% of the observed effect. Smaller target effects are harder to distinguish from background variability, so they require more participants. For example, for the primary half-dose comparison, planning for 75% of the observed effect gives 1,506 participants per arm for 80% power and 2,016 participants per arm for 90% power. These figures are illustrations based on that comparison's observed effect, not recommendations for this trial.

The assumptions describe a conventional two-arm planning calculation and do not establish that the method incorporates the crossover design or repeated observations. The trial's own sample-size assumptions and justification are not reported in the registry record. The plotted curve should be read as a visual expression of how the planning requirement changes with the assumed effect, not as additional observed trial evidence.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.320; pooled standard deviation σ = 2.351.
2. n = 2 × (1.96 + 0.842)² × 2.351² / 0.320² = 847.0, rounded up to 847 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.32                      # observed difference in means
sigma <- 2.35053185470863                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2766673)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 847 (80% power), 1,134 (90% power)
 75% of observed effect: n per arm = 1,506 (80% power), 2,016 (90% power)
 50% of observed effect: n per arm = 3,388 (80% power), 4,536 (90% power)
power.t.test: 847.9 
Simulated power at n = 847 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and one secondary outcome, and the posted results include comparisons of the full-dose group with the half-dose and saline groups. The record does not report a multiplicity plan, such as a correction across comparisons or a prespecified order in which hypotheses would be tested. The secondary comparison with an unadjusted p-value of 0.043 should therefore be interpreted cautiously rather than as a definitive finding. This concern is general: examining several outcomes and contrasts can increase the chance of a nominally notable result.

The record lists no reported analyses for the outcomes. It does not specify the sponsor's statistical model, the significance threshold used in the original analysis, how treatment periods were handled, or whether any interim analyses were planned. The original analysis plan and sample-size justification are not reported in the registry record. Those omissions prevent a direct assessment of whether the posted summaries reflect a prespecified analysis or how any deviations were handled.

Missingness is explicitly noted for the primary outcome. The description says that 2 subjects did not complete all 3 treatment groups and that some measurements were missed, leaving fewer than the potential observations. The record does not state the exact number of missing measurements, their reasons, whether missingness differed by treatment, or how incomplete treatment sequences were included in the analysis. It does not report a missing-data sensitivity analysis. General statistical principle: missing measurements can bias a comparison if their absence is related to the treatment or the unobserved outcome, and the direction of any such bias cannot be determined from the information reported.

The record also does not define whether the analysis followed an intention-to-treat, per-protocol, or other population. The 23 listed for each treatment group should not be taken as a complete explanation of which infants or measurements contributed to each endpoint. Without a reported analysis population and model, it is not possible to determine how the cross-over observations, missing pairs, or incomplete treatment groups were handled.

15. 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 serious adverse event summaries list 23 at risk in each treatment group and zero serious adverse events in each group. They also list zero other adverse events in each group and zero deaths in each group. No serious adverse event terms are listed. These figures describe what the registry record reports for the safety categories and groups.

A count of zero recorded events is not evidence that the risk is zero. With a limited number of participants and a short reported treatment period, uncommon events may not be observed. The record does not give further detail about the event definitions, ascertainment procedures, severity grading, or whether event collection covered periods beyond the treatment observation timeframe. It also does not report a comparison model or uncertainty intervals for safety outcomes.

The safety data should therefore be read as descriptive registry counts, not as proof that a treatment is free of adverse events or as a definitive comparison of safety between conditions. The reported figures cannot establish how the treatments would perform in a larger or different population.

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

The posted primary data show mean changes in expiratory flow of 0.38 L/min for full-dose albuterol, 0.7 L/min for half-dose albuterol, and 0.45 L/min for saline. The unadjusted summary-based contrasts are 0.32 L/min for half dose relative to full dose and 0.07 L/min for saline relative to full dose. Both primary confidence intervals include zero and are broad enough to include differences on either side of zero. The results therefore do not sharply distinguish the compared mean changes.

That pattern is not the same as demonstrating that the treatments have equal effects. A non-significant comparison can reflect uncertainty, and an equivalence conclusion would require an appropriate design, a prespecified margin, and a corresponding analysis. The registry record does not report an equivalence margin or a clinically meaningful threshold for EF75. The outcome values also describe short-term physiological measurements rather than a broad clinical outcome.

The secondary heart-rate summaries show a different pattern, including one unadjusted comparison with a confidence interval excluding zero. Because the outcome is secondary and no multiplicity approach is reported, that result should not be interpreted in isolation as confirmation of an effect. It does not answer the primary question about expiratory flow.

The record describes a randomized, triple-masked crossover design, but does not report the detailed analysis used for the posted outcomes. The simple recalculations from summary statistics do not account for all the information that a crossover analysis may use, such as within-infant relationships and treatment sequence. Missing measurements and incomplete treatment groups are also noted without a reported handling strategy. These limitations make the estimates less definitive than a fully specified, design-aware analysis would be.

Accordingly, the posted results are best understood as short-term descriptive evidence from the treatment conditions studied. They do not establish that albuterol does or does not produce a clinically important benefit, do not establish equivalence with saline, and do not determine longer-term effects or outcomes beyond the reported measurements.

17. Why This Trial Matters Statistically

This trial addresses a statistical problem that is common in neonatal and infant research: a treatment may be widely used even when the appropriate dose and the strength of evidence for a particular population remain uncertain. The registry summary describes the rationale as comparing an aerosol-literature-recommended dose with common local dosing practice and placebo. The study therefore puts dose selection and the value of a suitable comparator into a randomized design rather than relying only on routine practice.

The crossover structure is also statistically relevant. When the same infant contributes observations under different conditions, stable differences between infants may be less influential than in a comparison of separate groups. That potential advantage depends on design and analysis details, including the treatment order and the handling of repeated measurements. Those details are not reported in the registry record, illustrating why a design label alone is not enough to evaluate the analysis.

The primary results also show why effect estimates and confidence intervals matter alongside p-values. The mean contrasts are small relative to the reported variability, and their confidence intervals are broad and include zero. A non-significant result does not prove there is no difference; it can leave considerable uncertainty about what effects are compatible with the data. In a small study, such uncertainty is especially important when readers are tempted to treat a lack of statistical significance as evidence of equivalence.

Finally, the trial makes clear the distinction between a physiological endpoint and a clinical outcome. EF75 and heart-rate change are measurable over the stated treatment period, but the record does not report a threshold connecting these measures with meaningful longer-term outcomes. Interpreting them responsibly requires attention to measurement, repeated observations, missing data, and the limited precision of the contrasts—not just the treatment labels or the direction of a mean.

18. 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 posted evidence has limitations specific to the trial record. Enrollment was 24, and the outcome summaries list 23 for each treatment condition. The primary outcome description notes that 2 subjects did not complete all 3 treatment groups and that some measurements were missed. The number and pattern of missing measurements, the reasons for incomplete treatment, and the analysis strategy are not reported. This makes it difficult to determine how representative the posted means are of all intended measurements.

The study used a crossover design with repeated measurements, yet the record does not report the treatment sequence, any washout period, or a model accounting for within-infant correlation and treatment period. The posted contrasts are simple unadjusted recalculations from the summary statistics. They may not reflect all the information or assumptions that would enter a design-specific analysis. No sponsor-reported analysis is listed for the outcomes.

The reported endpoints are short-term physiological measures, with the stated timeframe extending every 4 hours in each treatment group up to 24 hours. The registry record does not report longer-term respiratory outcomes or a threshold for a clinically meaningful change in expiratory flow. Consequently, the results cannot establish whether the observed measurements correspond to changes that matter beyond the treatment observation period.

There is also no reported multiplicity strategy for the endpoint comparisons, no detailed statistical plan, and no reported justification for the original enrollment. The record does not describe which roles were masked, how the crossover sequence was generated, or how adverse events were collected. These reporting gaps do not show that the study failed to use such procedures; they mean that the relevant details are not reported in the registry record and cannot be evaluated from the posted information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Aerosolized Albuterol Use in Severe BPD — NCT02766673.
• Registry record last updated 2019-08-28; status last verified 2019-08.
• Results first posted 2019-07-30.
• 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.

22. Record Summary

NCT02766673, “Aerosolized Albuterol Use in Severe BPD,” is recorded as a completed randomized, triple-masked crossover trial sponsored by Children's Hospital of Philadelphia. Enrollment was 24. It compared full-dose albuterol, half-dose albuterol, and sterile saline administered by nebulizer and mechanical ventilator in infants with severe BPD.

The primary outcome was change in expiratory flow at 75% of vital capacity between pre- and post-treatment measurements, with a stated timeframe of every 4 hours in each treatment group up to 24 hours. The secondary outcome was percent change in heart rate. The primary posted comparisons have confidence intervals that include zero. The registry record notes incomplete treatment groups and missed measurements but lists no reported analyses. The available results are short-term descriptive data; the analysis plan and important crossover and missing-data details are not reported in the registry record.