Effect of Macrolide Antibiotics on Airway Inflammation in People With Chronic Obstructive Pulmonary Disease (COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Macrolide Antibiotics on Airway Inflammation in People With Chronic Obstructive Pulmonary Disease (COPD) (NCT00549445), a registered phase not stated study. The primary outcome is Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin..

2. Clinical Question

The study description frames the analysis as an assessment of the anti-inflammatory properties of azithromycin. It also refers to the frequency and severity of COPD exacerbations in its summary, but the listed primary outcome is PGP level, not an exacerbation outcome. These should not be treated as interchangeable questions. A biological marker can describe an inflammatory process, while an exacerbation outcome concerns clinical events; the listed endpoint alone cannot establish what happened to exacerbations.

3. Trial Design

The registry identifies this as a completed study sponsored by the University of Alabama at Birmingham, with enrollment of 53. The recorded start is 2007-08 and primary completion is 2011-07. The record describes an analysis of previously collected study data to examine azithromycin’s anti-inflammatory properties. Participants in the COPD Network Macrolide Study received either azithromycin or placebo for 1 year, according to the arm descriptions.

The analysis of interest uses samples collected during treatment. The registry reports 18 sputum samples from 13 placebo-treated participants and 14 sputum samples from 8 azithromycin-treated participants, collected at months 1 through 12. It says that sputum samples were not available for many participants and that this greatly reduced the sample size. The number of samples is not the same as the number of people: some participants contributed more than one sample. The record does not specify how repeated samples were handled in the analysis.

The registry explicitly notes that allocation was not stated and that the arms are not a like-for-like control comparison. The method of assigning participants to the arms is not reported in the registry record. Consequently, the design description does not support treating the arm contrast as a randomized treatment effect. Further details about eligibility criteria, masking, treatment adherence, and the parent study’s full design are not reported in the registry record.

The listed outcome is mean PGP level, in ng/mL, over a timeframe described as baseline to 12 months. Although the outcome title refers to sputum samples, its description says that nasopharyngeal swabs were obtained. This difference in specimen wording is not resolved in the registry record. The listed record contains one outcome measure and one analysis, but the analysis type is categorized as “other” and is not reduced to one comparison.

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: This research was conducted as an ancillary study to a multicenter trial (NCT00325897) of the efficacy of azithromycin treatment for 1 year in preventing chronic obstructive pulmonary disease (COPD) exacerbations to test whether sputum levels of proline-glycine-proline (PGP) were altered by treatment or associated with exacerbation frequency.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Levels of PGP from sputum samples are compared between subjects on the macrolide antibiotic, azithromycin, and subjects on placebo and correlated with neutrophil counts and protease activity in sputum.

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: The number of participants included in this study is small as sputum samples were available only from a minority of participants in the parent trial. Therefore, this greatly reduced the overall number of participants analyzed.

6. Primary Endpoint

The registry lists the primary outcome as Levels of PGP From Sputum Samples of COPD Patients Being Treated With Azithromycin., measured over Baseline to 12 months.

The primary endpoint concerns levels of PGP, in ng/mL, from samples collected from people with COPD receiving azithromycin or placebo. The registry describes PGP, including Neutrophil-PGP, as a marker of interest in airway inflammation. It also states that levels were to be compared between treatment groups and related to neutrophil counts and protease activity in sputum. The stated timeframe is baseline to 12 months.

Biomarkers can be used to study biological processes that may be relevant to a disease. In this case, PGP levels are intended to inform an assessment of neutrophilic inflammation and the biological effects associated with chronic azithromycin treatment. That purpose differs from directly measuring symptoms, exacerbations, or other clinical outcomes. A marker result alone does not establish a change in how participants felt or functioned.

The registry lists the outcome parameter as mean and the dispersion as full range. A mean describes the average value; a range describes the spread from the smallest to the largest observed value. Those summaries provide different information. The outcome description refers to both sputum samples and nasopharyngeal swabs, so the specimen wording is ambiguous in the registry record.

The registry record does not report the observed PGP values, the group means, the ranges, or an estimated treatment-group contrast. It therefore does not allow readers to assess the direction or magnitude of the observed endpoint result, or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying what was measured, which observations contributed, and what comparison the analysis was intended to make. The outcome listed in the registry is mean PGP level in ng/mL, with full range as the dispersion measure. The timeframe is baseline to 12 months. The description also refers to comparing treatment groups and relating PGP to neutrophil counts and protease activity in sputum. However, the registry does not give a single numerical estimate for the treatment-group contrast.

What does a mean and a range describe?

General statistical explanation: a mean is an average that combines the values in a set of observations into one summary. It can be useful for describing the central level of a measurement, but it does not show how values are distributed around that average. A range reports the lowest and highest values and gives a sense of the overall spread. It does not show whether most observations cluster near the mean or whether values are unevenly distributed. Since actual mean and range values are not reported in the registry record, the endpoint’s observed level and variability cannot be described.

The word “dispersion” refers to variation in the observations. The registry lists full range, but no range endpoints are reported. It also does not report a standard deviation, standard error, or other numerical measure of variability. The posted information therefore does not support reconstructing the endpoint’s uncertainty from summary statistics.

What would an effect estimate and confidence interval add?

General statistical explanation: an effect estimate expresses the size and direction of a comparison, such as a difference in mean values between groups. A confidence interval gives a range of values compatible with the data and the statistical procedure used. A narrower interval indicates greater precision than a wider interval, though interpretation also depends on the design and analysis. A confidence interval does not correct for a biased or non-comparable group contrast.

The registry does not report an effect estimate or confidence interval for PGP. It also does not report a p-value for the primary outcome. Thus, statistical evidence against a specified null hypothesis and the precision of the estimated contrast cannot be evaluated from the registry record. The absence of these values should not be replaced with assumptions based on the sample counts.

Why do repeated samples matter?

General statistical explanation: observations from the same participant often share characteristics and may be correlated. When repeated measurements are analyzed, a method may need to account for that within-participant dependence. Otherwise, an analysis that treats every sample as independent can give an inaccurate estimate of uncertainty. The registry reports 18 samples from 13 placebo-treated participants and 14 samples from 8 azithromycin-treated participants, collected across months 1 through 12. It does not report whether the analysis accounted for repeated samples, selected one sample per participant, or used another approach. The analysis method for repeated measurements is not reported in the registry record.

What does the sample-size planning language mean?

The registry describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. For time-to-event outcomes, the record says that illustrations would give the total number of events; for other outcomes, they would give participants per arm. The numeric planning results are not reported in the registry record.

General statistical explanation: a planning calculation estimates how many observations might be needed under specified assumptions to detect a chosen effect with a chosen probability. An illustration based on an observed effect is not the same as a design justification, and it is not observed power. The registry says these are planning illustrations, not the trial’s own design. The actual sample availability was reduced by missing sputum samples, and the record does not report the original sample-size justification or the assumptions behind the parent trial’s design.

What can be learned from a normal approximation?

General statistical explanation: a normal approximation uses properties of the normal distribution to estimate uncertainty or sample-size needs. Its usefulness depends on whether the data and analysis meet the assumptions relevant to that approximation. It does not itself establish that an analysis is appropriate. For a biological measurement, features such as skewness or unusually influential values may affect how well a mean-based approximation describes the data. No distributional diagnostics or model details are reported in the registry record, so whether the approximation fits these observations cannot be assessed.

Over-dispersion is a general term for data varying more than a statistical model expects. If a model assumes less variability than is present, uncertainty can be understated and intervals or tests can be unreliable. This is a general consideration rather than a reported finding in this study: the registry record provides no model diagnostics or variability estimates with which to assess over-dispersion.

Finally, the record labels the analysis type as “other” and says it is not reduced to one comparison. That classification does not identify the statistical procedure. The model specification, covariate adjustment, handling of missing samples, and inferential procedure are not reported in the registry record. Accordingly, methodological details beyond the stated planning assumptions cannot be reconstructed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. That count does not establish that only one statistical question was considered during the full study or that no multiplicity adjustment was needed. The analysis description mentions comparing PGP levels between treatment groups and correlating PGP with neutrophil counts and protease activity. The number of statistical tests conducted for those aims and any strategy for controlling multiplicity are not reported in the registry record.

General statistical explanation: when many outcomes, comparisons, or analyses are examined, the chance of obtaining an apparently unusual result by chance can increase. A prespecified analysis plan and an appropriate multiplicity strategy can help clarify how results should be interpreted. The protocol, prespecification details, and multiplicity plan are not reported in the registry record. It is therefore not possible to determine whether the listed analysis was the sole planned analysis or how any additional analyses were handled.

Missing sample availability is a direct limitation. The description states that sputum samples were unavailable for many participants and that this greatly reduced the sample size. It reports the available samples and contributing participants by arm, but does not explain why samples were unavailable, whether missingness differed between arms, or how missing observations were handled. The approach to missing data is not reported in the registry record.

The analysis population is also not fully characterized. The record does not say whether all participants with available samples were included, whether any samples were excluded, or whether the analysis followed a prespecified population definition. The analysis population and exclusion rules are not reported in the registry record. Because allocation was not stated and the arms are described as not like-for-like, the extent to which the available participants represent comparable groups is also uncertain.

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 3% reporting threshold.

The registry reports serious adverse event figures separately for azithromycin-treated and placebo-treated participants. For the azithromycin-treated group, 8 participants were at risk, with 0 affected by a serious adverse event and 0 deaths reported. For the placebo-treated group, 13 participants were at risk, with 0 affected by a serious adverse event and 0 deaths reported. No serious adverse event terms are listed.

These figures describe the participants included in the reported safety groups. They do not establish that no serious adverse events could occur, nor do they show that the treatments have equivalent safety. The groups are small, allocation was not stated, and the record does not provide further detail about safety monitoring, event definitions, follow-up completeness, or non-serious adverse events. Those details are not reported in the registry record.

Zero reported events should be read as a count in the registry, not as proof of zero risk. The safety figures also concern a different outcome from the primary PGP endpoint. They do not answer whether PGP levels differed between groups or describe exacerbation outcomes. The serious adverse event counts can be reported as recorded, while recognizing that the available record does not support broader conclusions about comparative safety.

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

The registry record identifies an analysis of PGP levels in samples collected from participants with COPD treated with azithromycin or placebo. It reports the number of samples and participants contributing to each arm and notes that unavailable sputum samples greatly reduced the sample size. It also describes the intended biological question: whether PGP levels differ between arms and how they relate to neutrophil counts and protease activity in sputum.

The record does not report the actual PGP results. Without group values or an estimated contrast, it is not possible to say which arm had higher levels, how large any difference was, or how precisely a difference was estimated. The data posted in the registry therefore do not support a conclusion about the direction or strength of the primary endpoint comparison.

Even if a numerical biomarker contrast were available, interpretation would require attention to the study design. Allocation was not stated, and the record warns that the arms are not a like-for-like control comparison. A difference between groups would not, on this information alone, demonstrate that treatment caused the difference. The record also does not describe how repeated samples from the same participant or missing samples were handled in the analysis.

The primary endpoint is a biomarker measure rather than a direct measure of symptoms or exacerbations. The study summary mentions COPD exacerbations, but the listed primary measure is PGP. A result for PGP would not, by itself, establish an effect on exacerbation frequency or severity. The registry does not report those outcomes as part of the listed primary result.

The safety listing records zero serious adverse events in each group, among the participants at risk as reported. Those counts do not establish absence of risk or equivalence between groups. Overall, the record provides a limited account of the study question, available samples, and serious adverse event counts, but not the numerical primary outcome evidence needed to judge the biological comparison.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an analysis population can differ substantially from a study’s overall enrollment. The registry reports enrollment of 53, but the primary outcome description includes sputum samples from 13 placebo-treated participants and 8 azithromycin-treated participants. It explicitly attributes the reduction in sample size to unavailable samples. Readers should distinguish the broader enrollment figure from the smaller set of participants contributing to this biomarker analysis.

The record also illustrates why sample counts and participant counts should not be conflated. It reports 18 samples from the placebo-treated participants and 14 from the azithromycin-treated participants. Multiple samples came from some participants, so the independence of observations is a relevant analytical issue. The registry does not explain how repeated observations were handled.

Design information matters alongside outcome summaries. Allocation was not stated, and the record cautions that the arms are not a like-for-like control comparison. This limits causal interpretation even before considering the missing numerical endpoint results. The study’s stated biological objective is also distinct from the exacerbation aims mentioned in the summary, emphasizing the importance of matching conclusions to the outcome actually reported.

Finally, the registry record shows the limits of interpreting a statistical analysis when the outcome values, effect estimate, uncertainty interval, and analysis details are absent. A listed endpoint and sample count do not substitute for a result. The record can establish what was intended to be measured and describe some features of the available data, while leaving the central numerical comparison unresolved.

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 most direct limitation is that the registry record does not report the PGP outcome values or a treatment-group estimate. No numerical means, full ranges, confidence interval, or p-value are reported. Consequently, the magnitude, direction, and precision of the primary comparison cannot be assessed.

Available samples were limited because sputum was unavailable for many participants. The record gives counts of samples and contributing participants, but does not describe the reasons for missing samples or whether their availability was related to treatment group or participant characteristics. Missing-data handling is not reported in the registry record.

The analysis may include repeated samples from individual participants, as the number of samples exceeds the number of participants in each group. The statistical handling of within-participant dependence is not reported in the registry record. Without that information, the precision of any analysis cannot be evaluated.

Allocation was not stated, and the registry cautions that the arms are not a like-for-like control comparison. This limits interpretation of any between-group contrast as a treatment effect. Further details about group comparability, adjustment, and analysis populations are not reported in the registry record.

There is also ambiguity in the specimen description: the outcome title refers to sputum samples, while the description says nasopharyngeal swabs were obtained. The record does not resolve this discrepancy. It lists mean as the outcome parameter and full range as dispersion but gives neither numerical summary. The analysis is categorized as “other,” and its specific statistical method is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Macrolide Antibiotics on Airway Inflammation in People With Chronic Obstructive Pulmonary Disease (COPD) — NCT00549445.
• Registry record last updated 2017-09-29; status last verified 2017-08.
• Results first posted 2017-08-14.
• 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 record concerns an analysis of PGP levels in samples from people with COPD who received azithromycin or placebo for 1 year. The study is marked completed, with enrollment of 53. The primary outcome is mean PGP level in ng/mL over baseline to 12 months, with full range listed as the dispersion measure.

The outcome description reports 18 sputum samples from 13 placebo-treated participants and 14 samples from 8 azithromycin-treated participants. It says that unavailable sputum samples greatly reduced the sample size. The specimen wording is inconsistent because the description also refers to nasopharyngeal swabs. Allocation was not stated, and the registry cautions that the arms are not a like-for-like control comparison.

Numerical PGP results and the statistical method are not reported in the registry record. The safety listing reports 0 serious adverse events and 0 deaths in each group, among 8 azithromycin-treated and 13 placebo-treated participants at risk.