Bosentan for Poorly Controlled Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bosentan for Poorly Controlled Asthma (NCT00815347), a randomized phase 2 study. The primary outcome is Change in FEV1.

2. Clinical Question

The clinical question concerns whether adding bosentan to treatment for asthma symptoms is associated with a change in lung function. The brief summary describes the study hypothesis as an improvement in symptoms and physiology among people who remained symptomatic despite controller therapy. The designated primary outcome is narrower: change in FEV1, a measure of the volume of air exhaled forcefully, assessed after dosing. FEV1 is a physiological endpoint; it is not itself a direct measure of symptoms or overall asthma control.

The trial also lists rescue beta-agonist use and the Asthma Control Test Questionnaire as secondary outcomes. These address different aspects of asthma experience and management. The record does not provide their results, nor does it report results for the primary endpoint. Consequently, the posted information does not establish the direction or magnitude of any treatment-associated change. It also does not allow a statistical comparison of bosentan with placebo for FEV1 or the secondary outcomes.

The registry lists enrollment as 11, while the brief summary describes an intended group of 20 participants. Those are distinct record statements: the enrollment field describes the registered enrollment, whereas the summary describes the planned study population. The registry status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain why the study stopped or how much of the planned protocol was completed.

3. Trial Design

The registry describes a randomized, triple-masked, crossover trial of bosentan and placebo. In a crossover design, participants receive more than one study treatment in sequence, allowing comparisons within participants as well as across treatment sequences. Randomization is intended to reduce systematic differences in which treatment participants receive first. Triple masking indicates that the registry classifies the trial as masked at three levels, but the identities of those masked are not reported in the registry record.

The brief summary describes two treatment periods, each lasting 8 weeks, with participants switching from their initial treatment to the other. It states that the initial 4 weeks would be at half the final dose, followed by the final dose, and describes testing acute bronchodilator effects on the first day at the full therapeutic dose. The official title calls the trial a 17 Week crossover trial. These descriptions do not align completely in their stated duration; the registry record does not explain the difference. The actual treatment sequences completed by participants are not reported in the registry record.

The trial is listed as Phase 2, with asthma as the condition and bosentan and placebo as the interventions. UConn Health is named as the sponsor. The registry lists a start of 2008-12 and primary completion of 2010-09, and gives the status as terminated. Enrollment is listed as 11. These registry entries should not be taken to establish that every enrolled participant completed every treatment period or every measurement; completion and analysis populations are not reported in the registry record.

The primary outcome is change in FEV1, measured in liters, with a mean and 95% confidence interval specified as the summary format. The stated measurement times are 1, 2, and 4 hours after dosing. This acute measurement schedule is distinct from the longer treatment periods described in the brief summary. The record also lists nine outcome measures, including secondary outcomes of FEV1, rescue beta-agonist use, and the Asthma Control Test Questionnaire, but it does not report results for these measures.

A crossover design can be efficient because each participant can contribute measurements under both treatments. It also requires attention to treatment order, period effects, and possible carryover from one treatment period into the next. The registry record does not report the planned statistical model or how those design issues were to be addressed. It does not report a sample-size justification, or whether the intended enrollment changed during the trial.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in FEV1, measured over 1, 2, 4 hours after dosing.

The primary endpoint is change in FEV1, expressed in liters, with measurements specified at 1, 2, and 4 hours after dosing. FEV1 is the volume of air that a person can forcefully exhale during the first second of an expiration. It is commonly used as a physiological measure of airflow limitation and lung function. A change in this measure can describe an acute change in airway function, but it does not capture every aspect of asthma symptoms or control.

The registry specifies a mean and a 95% confidence interval as the summary format. In general, a mean describes the average measured value or change in a group. A confidence interval conveys uncertainty around an estimate: it gives a range of values compatible with the data and the statistical method used. It is not a guarantee that the true effect lies in that range, and its interpretation depends on the study design and analysis.

The three stated measurement times matter because the acute response may vary over time after dosing. They should be treated as separate assessment times unless the analysis plan specifies a combined outcome or another approach. The record does not report such an analysis plan, nor does it identify a single time point as more important than the others.

No observed FEV1 means, changes, confidence intervals, or treatment comparisons are reported in the registry record. Therefore, the endpoint definition explains what the trial intended to measure, but it does not allow a conclusion about the observed size, direction, or precision of a treatment difference. The record also does not report a clinically meaningful threshold for change in FEV1.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas are relevant to reading this trial record, even though the registry does not report its analysis methods or outcome estimates. The points below are general explanations and should not be mistaken for a description of analyses confirmed to have been used in this trial.

What does a crossover design compare?

In a crossover design, participants receive different treatments in sequence. The comparison can use measurements from the same participant under bosentan and placebo. In general, this can account for stable participant characteristics that might otherwise contribute to variation between treatment groups. The design still depends on valid measurement in each period and appropriate handling of the sequence and timing of treatment.

Period effects are changes that occur over time regardless of treatment, such as changes in symptoms or measurement conditions. Carryover is an effect of an earlier treatment that persists into a later period. If carryover is present, a later-period measurement may reflect more than the treatment assigned for that period. A suitable analysis may need to account for period and sequence, and the protocol may specify a washout or other approach. Whether the trial planned a washout, assessed carryover, or modeled period and sequence is not reported in the registry record.

What does randomization contribute?

Randomization assigns treatment order using a chance-based process. In general, it helps prevent systematic differences in assignment, including which sequence participants receive. It does not guarantee that every feature of a small enrolled group will be balanced, and it does not by itself address missing measurements, protocol deviations, or carryover. The record identifies the trial as randomized but does not report the randomization method, allocation concealment, or the number assigned to each sequence.

What does masking mean?

The registry classifies the trial as triple-masked. Masking is intended to limit the influence of treatment knowledge on participant experience, study conduct, or outcome assessment. The registry does not specify which roles were masked or describe how masking was maintained. The classification therefore identifies the stated masking level, but does not provide enough detail to evaluate its implementation.

How should the mean and confidence interval be read?

The primary endpoint is a continuous measure, and the record specifies the mean with a 95% confidence interval. A mean is an average that summarizes measured values; it does not show how much individual observations vary. A confidence interval describes uncertainty in an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. Neither the mean nor interval is reported for the primary outcome in the registry record, so this interpretation cannot be applied to an observed treatment estimate.

In general, the analysis of a crossover endpoint should reflect the repeated measurements within each participant rather than treating all observations as independent. A model may account for treatment, period, sequence, and participant-level variability. The exact model, assumptions, and method for estimating the treatment effect are not reported in the registry record. It would be inappropriate to assign a specific model to this trial based only on its design label.

Why do time points and multiple outcomes matter?

The primary endpoint lists measurements at 1, 2, and 4 hours after dosing. These are multiple time points for assessing the same type of measure. If each time point is tested separately, the collection of tests raises a multiplicity concern: the chance of at least one apparently unusual result can increase as the number of tests grows. An analysis plan can address this by defining a primary time point, adjusting inference, or treating results as descriptive. The registry record does not report which approach, if any, was planned.

The record lists nine outcome measures, including secondary measures of FEV1, rescue beta-agonist use, and the Asthma Control Test Questionnaire. Outcomes can differ in scale and meaning, and analyses across multiple outcomes may require prespecified priorities or adjustments. The registry does not report the planned testing hierarchy, multiplicity adjustment, or which outcomes were analyzed. It records zero analyses, so no outcome-specific statistical results are available there.

What is over-dispersion in general?

Over-dispersion occurs when observed variability in data is greater than a statistical model assumes. It is especially relevant to some count outcomes, where a simple model may underestimate variability and produce overly narrow uncertainty intervals or overly optimistic tests. The primary endpoint in this trial is a continuous FEV1 measure, not a count outcome. The record does not describe an analysis that would make over-dispersion a stated issue for the primary endpoint; this concept is a general statistical consideration rather than a reported trial method.

What can planning calculations tell readers?

A sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis. The record describes an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such an illustration is not the trial’s own sample-size justification and cannot establish the power of the completed study. The record does not report the trial’s sample-size justification. No sample-size calculation should be interpreted as observed power.

The distinction between a planning illustration and a completed analysis is important. A planning calculation asks what sample size might be needed under assumptions. An outcome analysis estimates what was observed and how uncertain that estimate is. The registry record does not report the primary-outcome estimates needed to judge precision or to derive an effect-based planning illustration. Any sample-size planning values associated with posted results should therefore be understood as hypothetical planning aids, not as evidence that the treatment effect was demonstrated.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies change in FEV1 as the primary outcome and lists measurement times of 1, 2, and 4 hours after dosing. It also lists secondary outcomes of FEV1, rescue beta-agonist use, and the Asthma Control Test Questionnaire, within a total of nine outcome measures. The record does not describe which secondary outcomes were analyzed, how the time points were prioritized, or whether any adjustment for multiple testing was planned or used. In general, testing multiple outcomes or time points without a prespecified strategy can make isolated findings harder to interpret.

The record gives no outcome analysis results. It does not report participant-level missingness, missing measurements by treatment period, reasons for missing data, or a method for handling missing observations. In a crossover study, missing data can affect whether within-participant comparisons are possible and may leave treatment periods unevenly represented. The amount and pattern of missingness are not reported in the registry record.

The analysis population is also not specified. Enrollment is listed as 11, but the record does not state how many participants were randomized to each sequence, completed each period, or contributed measurements to the primary endpoint. It does not identify an intention-to-treat, per-protocol, or other analysis set. The trial status is terminated, but that status does not establish which participants or measurements were included in an analysis.

These omissions limit interpretation: readers cannot assess the effect of missing data, reproduce the intended analysis, or determine how multiplicity was handled. The reason for termination and any interim analyses are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: abnormal liver function blood tests (9.1%).

The serious adverse event figures are descriptive counts reported for the treatment groups. For bosentan, the record lists 9 at risk and 0 serious adverse events. For placebo, it lists 11 at risk and 1 serious adverse event. The record also lists abnormal liver function blood tests as the top serious term, at 9.1%. The term is reported in the registry record without enough detail to infer its timing, severity beyond its classification as serious, or treatment attribution.

These figures should not be read as a definitive comparison of safety between bosentan and placebo. The record does not report statistical comparisons, follow-up completeness, event narratives, or whether participants had the same opportunity for observation under each treatment. That information is especially relevant in a crossover trial, where participants receive treatments in sequence. The listed at-risk figures do not establish how many participants completed each period or contributed to the efficacy analysis.

Other adverse events are not characterized in the posted information beyond the recorded fields. Death counts are not reported in the registry record. The available serious-event figures therefore describe what is listed, but cannot provide a comprehensive account of all adverse events or establish whether an event was caused by a study treatment.

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

The registry record establishes that a randomized, triple-masked crossover trial was registered to study bosentan and placebo in people with asthma. It specifies change in FEV1 as the primary endpoint and identifies measurements in liters at 1, 2, and 4 hours after dosing. It also lists secondary outcomes, gives enrollment as 11, and reports the trial status as terminated. Those details define the question and some features of the study, but do not show the observed treatment effect.

No primary-outcome estimates, confidence intervals, p-values, or analysis results are reported. The record therefore cannot establish whether FEV1 changed, whether change differed between bosentan and placebo, or how precise any estimated difference would be. It also cannot answer whether secondary measures changed or how those outcomes compared. The absence of registry results is not evidence of no effect, and it is not evidence of equivalent effects.

The serious adverse event entries provide limited descriptive information: 0 serious events are listed for bosentan among 9 at risk, and 1 is listed for placebo among 11 at risk. The record’s top serious term is abnormal liver function blood tests at 9.1%. These entries do not establish a causal relationship or support a reliable treatment safety comparison. The information needed to interpret event timing, exposure, and completeness is not reported in the registry record.

General interpretation of crossover evidence would require attention to period effects, sequence, carryover, and missing observations, in addition to the treatment comparison itself. The registry record does not report the statistical model or its assumptions. It also does not report how multiplicity across the stated times and outcomes was addressed. Consequently, the trial’s design can be described, but its statistical findings cannot be evaluated from the posted outcome information.

The brief summary describes a planned population of 20, while the registry lists enrollment as 11. The reason for the difference, the number completing both periods, and the analysis population are not reported. The stated termination status likewise does not explain why the trial ended. These gaps matter because they prevent a full assessment of trial conduct and the amount of information available for the intended comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a crossover design with an acute physiological endpoint. A crossover can allow within-participant comparisons, which may help distinguish treatment-associated changes from stable differences between participants. At the same time, interpretation relies on adequate measurements across treatment periods and consideration of treatment order, period effects, and carryover. The registry record identifies the design but does not report how those issues were handled.

The primary outcome has repeated post-dose assessment times. Such timing can be informative about how an acute response develops, but it also raises questions about which time point drives the primary inference and how multiple comparisons are managed. The registry gives the measurement schedule, but does not report a statistical plan for those time points. The trial also lists nine outcomes, making prespecification and multiplicity relevant general considerations.

The record’s gap between its planned population description and listed enrollment is also important to statistical interpretation. The brief summary describes 20 intended participants, whereas the registry lists enrollment as 11. The record does not explain the difference or report the number analyzed. Without outcome estimates and analysis-population details, the precision and robustness of any intended treatment comparison cannot be assessed.

Finally, the record illustrates the distinction between a defined research question and an interpretable result. It identifies the treatments, population, design, primary measure, and timing, but gives no primary-outcome analysis. Statistical conclusions require estimates and uncertainty, not only a design description. The limited safety figures likewise require careful descriptive reading rather than a broad comparative conclusion.

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 of the registry record is the absence of primary and secondary outcome results. It gives no FEV1 means, changes, treatment contrast, confidence interval, or p-value. Without these, the size, direction, and precision of any treatment effect cannot be assessed. The record lists nine outcomes but does not provide their results or indicate which were analyzed.

The registered descriptions also leave some design details unresolved. The official title describes a 17 Week trial, while the brief summary describes two 8-week treatment periods and an initial 4 weeks at half the final dose. The record does not explain the difference between these descriptions. It does not report treatment sequences actually completed, a washout approach, or how period and carryover effects were handled.

The brief summary describes an intended group of 20 participants, while enrollment is listed as 11. The reason for the difference is not reported. The record does not state how many participants completed both periods, had primary-outcome measurements, or entered an analysis. It also does not report missing-data patterns, analysis populations, or reasons for missing measurements.

The registry status is terminated, but the reason for termination and any interim analyses are not reported in the registry record. The sample-size justification and statistical analysis plan are also not reported. The stated planning illustration is not a substitute for either of these, and it cannot establish observed power. These limitations mean the registered design and limited safety counts can be described, but the trial’s efficacy findings and the completeness of its analyses cannot be independently assessed from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bosentan for Poorly Controlled Asthma — NCT00815347.
• Registry record last updated 2012-10-01; status last verified 2012-09.
• Results first posted 2012-10-01.
• 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 describes a Phase 2 randomized, triple-masked crossover trial of bosentan and placebo for asthma, sponsored by UConn Health. The official title calls it a 17 Week trial; the brief summary describes two 8-week treatment periods. The registry lists enrollment as 11, a start of 2008-12, primary completion of 2010-09, and status as terminated.

The primary outcome is change in FEV1 in liters, summarized as a mean with a 95% confidence interval at 1, 2, and 4 hours after dosing. Secondary outcomes include FEV1, rescue beta-agonist use, and the Asthma Control Test Questionnaire. No outcome analysis results are reported in the registry record. Serious adverse event entries list 0 events among 9 at risk for bosentan and 1 among 11 at risk for placebo; abnormal liver function blood tests are listed as the top serious term at 9.1%. The reason for termination and the analysis population are not reported.