Effects of N-acetylcysteine on Cardiorespiratory Control in COPD Patients With Mild-to-moderate Airflow Obstruction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of N-acetylcysteine on Cardiorespiratory Control in COPD Patients With Mild-to-moderate Airflow Obstruction (NCT02579772), a randomized phase 4 study. The primary outcome is Plasma Redox Status - Circulating Glutathione.

2. Clinical Question

The registry describes a broader purpose: determining whether N-acetylcysteine improves central and peripheral cardiorespiratory control and physical capacity. The posted primary endpoint is narrower than that overall purpose. It is a laboratory measure, rather than a direct measure of exercise capacity, symptoms, or clinical events.

The record lists additional outcomes involving cardiac output, skeletal muscle deoxygenation, capillary blood flow dynamics, pulmonary oxygen uptake, and minute ventilation. These describe physiological domains relevant to the study's broader question, but their inclusion does not establish that results for each outcome are available or statistically conclusive. The registry record reports five secondary outcomes and zero analyses. It does not report a primary treatment-effect estimate or an inferential test for the primary endpoint.

The trial is described as randomized and crossover. In general, a crossover study compares treatment periods within participants, which can make paired responses important to interpretation. The registry record does not report the treatment sequence, period-specific analysis, or the participant-level pairing available for the posted primary summaries. Therefore, the arm means alone do not show how the treatment contrast was estimated.

3. Trial Design

The record identifies NCT02579772 as a completed Phase 4 study with randomized allocation, triple masking, and a crossover model. It lists Queen's University as the sponsor. The recorded study start is 2015-07, and primary completion is 2016-05. The enrollment is 13.

The two interventions were N-acetylcysteine pills and placebo pills. In a crossover design, participants receive more than one intervention over different periods, so their outcomes can be compared across treatment conditions. General: this design can account for stable differences between participants when the analysis uses within-participant comparisons. It also makes period effects, treatment order, and the handling of paired observations relevant. The sequence, any washout period, period duration, and analysis of treatment order are not reported in the registry record.

The record labels masking as triple but does not identify which groups of people were masked or describe how masking was maintained. Random allocation is recorded, but the method used to generate the sequence and the process for concealing allocation are not reported in the registry record. These details matter for evaluating how the design was implemented; their absence from the record does not establish that a particular procedure was or was not used.

The overall enrollment and the posted primary outcome summaries have different counts: each intervention summary reports n=9. The record does not explain why the outcome summaries include fewer participants than the enrollment, whether participants contributed data to both intervention summaries, or whether all paired observations were available. It also does not report participant flow or the analysis population used for the endpoint.

The stated endpoint was collected before exercise on day 4 of each experimental arm. The record does not specify the timing or details of other visits, the length of treatment exposure, adherence, or concomitant treatments. A sample-size justification and the trial's statistical analysis plan are not reported in the registry record. These unknowns constrain assessment of whether the reported endpoint and summaries follow the intended protocol.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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 Plasma Redox Status - Circulating Glutathione, measured over pre-exercise value (day 4).

The primary endpoint is circulating plasma glutathione, measured in micromolar, using fluorescent detection of plasma samples collected before exercise on day 4 of each experimental arm. The registry labels the endpoint as plasma redox status and specifies that measurements were taken in the placebo and N-acetylcysteine conditions.

Glutathione is used as a biochemical indicator related to redox status, the balance of oxidation and reduction processes. General: a laboratory marker can help characterize a biological response to an intervention, but a change in a marker is not by itself evidence of a change in symptoms, function, or clinical outcomes. This endpoint therefore addresses a mechanistic or physiological question, not the entirety of the study's broader stated aim concerning cardiorespiratory control and physical capacity.

The posted summaries give a mean and standard error for each intervention. The N-acetylcysteine mean is 8.97 micromolar with a standard error of 0.61, based on n=9. The placebo mean is 7.05 micromolar with a standard error of 0.49, based on n=9. These are arm-level summaries. The registry record does not report a paired treatment contrast, confidence interval, or statistical test for this endpoint, so the summaries alone do not establish the precision or statistical significance of a treatment effect.

The record does not report a clinically meaningful threshold for glutathione or explain what magnitude of change would be important. Thus, the endpoint can be read as a measure of circulating glutathione under the specified sampling conditions, but its clinical interpretation is not established by the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized as a mean with standard error. Its analysis count is zero, and it does not post an inferential estimate for the treatment comparison. The methods below explain how to read the posted statistics and which information would be needed for a fuller assessment. General statistical explanations are identified as general.

What does a mean describe?

A mean is a measure of the central level of a continuous outcome. The primary outcome summaries report a mean of 8.97 micromolar for N-acetylcysteine and 7.05 micromolar for placebo. These values describe the posted observations in each condition; they are not individual participant values. A mean can be influenced by the distribution of observations, and the registry record does not report the individual measurements or their distribution.

What does the standard error describe?

The standard error describes the estimated precision of a sample mean. The posted standard errors are 0.61 for N-acetylcysteine and 0.49 for placebo. General: the standard error is different from a standard deviation, which describes variability among individual observations. A standard error alone is not a confidence interval and does not give a complete account of uncertainty about the treatment contrast. The record does not report standard deviations or a confidence interval for the primary comparison.

Why is the crossover structure important?

General: in a crossover design, participants receive multiple treatment conditions over time, and the analysis can compare their outcomes across conditions. Such a comparison uses the pairing of measurements from the same participant. The precision of a paired comparison depends in part on how closely related the participant's measurements are across periods. Separate arm means and standard errors do not reveal that relationship.

The registry identifies the study as crossover but does not report treatment sequences, period effects, a washout period, or the statistical model. It also does not report a mean paired difference. The record therefore does not allow readers to verify whether the analysis accounted for within-participant pairing, treatment period, sequence, or other design features. Those methods should not be inferred from the crossover label alone.

What can be concluded without a test or interval?

A treatment-effect estimate expresses the contrast between conditions under a specified analysis. A confidence interval communicates the range of estimates compatible with the data and model at a chosen confidence level. A p-value evaluates how compatible the observed data are with a statistical null hypothesis, under the assumptions of the test. General: neither a p-value nor a confidence interval alone determines clinical importance.

No primary treatment-effect estimate, confidence interval, or p-value is reported in the registry record. The fact that the N-acetylcysteine mean is higher is a description of the observed summaries, not a substitute for a paired estimate and its uncertainty. The absence of an inferential result does not establish either a difference or equivalence.

How should the sample-size illustrations be read?

The sample-size illustrations are planning calculations based on the observed effect, rather than the trial's own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. General: such calculations describe hypothetical participant requirements under specified assumptions; they are not observed power and do not show the probability that the completed trial detected an effect. The sample-size justification used when designing this trial is not reported in the registry record.

These calculations depend on the effect used as their starting point and on the assumptions used to model uncertainty. When based on an observed effect, planning illustrations can change substantially if the observed estimate is imprecise. The registry record does not report an independent target effect or rationale for the trial's enrollment, so the illustrations should not be read as evidence that the study was adequately powered for its primary endpoint.

Why can over-dispersion matter?

General: over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not accommodate the extra variability. The primary endpoint is continuous, and no over-dispersion analysis is reported. The record does not provide enough distributional or model information to determine whether this issue was assessed. It should not be assumed that over-dispersion occurred.

Overall, the posted means and standard errors support a descriptive reading of the outcome summaries. A design-aware treatment estimate, its uncertainty, and a clear account of the analysis population would be needed for stronger statistical interpretation. Those items are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("N-acetylcysteine", "Placebo")
n   <- c(9, 9)
m   <- c(8.97, 7.05)
sp  <- c(0.61, 0.49)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  N-acetylcysteine  9  8.970  1.830  7.563  10.377
CARM  Placebo  9  7.050  1.470  5.920  8.180

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and names five secondary outcomes. These include changes in cardiac output, skeletal muscle deoxygenation dynamics, capillary blood flow dynamics, pulmonary oxygen uptake dynamics, and minute ventilation. The registry reports zero analyses. Results and inferential tests for these secondary outcomes are not reported in the registry record.

When a study examines multiple outcomes, the chance of at least one apparently unusual result can increase if each result is tested independently. General: multiplicity methods can address this issue, but they require a prespecified testing strategy and clear reporting. The registry record does not report whether multiplicity adjustments were planned or used, how outcomes were prioritized beyond identifying the primary endpoint, or whether any interim analyses occurred.

The primary summaries include n=9 for each intervention, compared with an overall enrollment of 13. The record does not explain the difference or describe the analysis population. It does not report whether participants had missing measurements, how missing values were handled, whether all participants contributed paired data, or whether analyses followed an intention-to-treat or another approach. These missing details limit assessment of selection and missing-data bias.

A statistical analysis plan and protocol-level rules for handling missing outcomes are not reported in the registry record. The number of outcomes listed should not be taken to mean that every outcome was analyzed or that any particular adjustment was applied. Without the planned and implemented analysis details, the effect of multiplicity and missing data on interpretation cannot be determined.

12. 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 non-serious adverse event terms

The safety summaries report serious adverse events for n=9 at risk in each condition. Zero serious adverse events are recorded for N-acetylcysteine, and zero for placebo. These are counts in the registry's posted summaries; they do not establish that no events occurred outside the reported observation or ascertainment period.

For other adverse events, the record reports one affected participant among n=9 at risk in the N-acetylcysteine condition and zero among n=9 at risk in the placebo condition. The record does not provide event terms for this other adverse event. No top serious adverse-event terms are listed. Death counts are not reported in the registry record.

General: safety counts are descriptive and depend on how events were defined, collected, and attributed. The registry record does not report those procedures, the observation period for adverse events, or details about severity and relatedness. With a small number of participants represented in the safety summaries, the counts provide limited information about uncommon events. Zero recorded serious events should not be interpreted as proof of no risk, and the observed other-event count does not establish a causal relationship to either condition.

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

The posted primary outcome data describe plasma glutathione before exercise on day 4 of each experimental arm. The N-acetylcysteine condition has a mean of 8.97 micromolar with standard error 0.61, and the placebo condition has a mean of 7.05 micromolar with standard error 0.49. The registry reports n=9 for each summary. These figures show the reported arm-level values and their standard errors.

They do not provide a paired treatment estimate, confidence interval, or p-value. Because the study is described as crossover, the within-participant relationship may be important to the treatment comparison. The registry record does not describe the analysis used to account for that structure. The means alone therefore do not establish the size or precision of the treatment effect, nor whether an inferential comparison supports a difference.

The result also does not establish whether a difference in plasma glutathione would correspond to a meaningful change in cardiorespiratory control, physical capacity, symptoms, or other clinical outcomes. The registry's stated study purpose is broader than the posted primary endpoint. Results for the listed secondary outcomes are not reported in the registry record.

The posted summaries are not a basis for concluding that the interventions are equivalent, that one is clinically preferable, or that an outcome would be reproduced in another population or setting. The enrollment is 13, while each primary summary includes n=9; reasons for this are not reported. Missing-data handling, the analysis population, and the statistical plan are also not reported.

Accordingly, the record supports a descriptive account of the endpoint values, but not a complete assessment of treatment effect or clinical importance. Any interpretation should remain limited to the recorded measure, sampling time, and summaries, with the uncertainty about analysis and participant inclusion kept explicit.

14. Why This Trial Matters Statistically

Statistically, the trial is notable because it uses a randomized crossover design to study a continuous physiological measure. General: a crossover structure can make within-participant comparisons informative, since each participant can contribute measurements under more than one condition. It also means that the analysis must account appropriately for pairing and for possible period or sequence effects. The registry record identifies the design but does not report how those features were handled.

The record illustrates the distinction between descriptive summaries and a treatment-effect analysis. It reports a mean and standard error in each condition, but no paired contrast, confidence interval, or p-value. The direction of the arm means is visible from the posted values, yet the uncertainty of the treatment comparison cannot be judged from those summaries alone. The primary endpoint is a biomarker, so it also raises the general distinction between a measurable physiological response and an outcome that directly reflects how participants feel or function.

The discrepancy between enrollment of 13 and outcome summaries based on n=9 in each condition is important for transparency. The record does not explain participant inclusion or missing observations. In a crossover study, knowing whether the same participants contributed to both conditions is especially relevant for interpreting the summaries and assessing precision.

The registry lists several additional physiological outcomes but reports zero analyses. That gap makes it difficult to evaluate the broader stated study purpose or the role of multiple outcomes in the planned interpretation. The sample-size illustrations are planning calculations based on the observed effect and do not replace an original sample-size justification or an analysis of the completed trial's uncertainty.

The trial therefore highlights why design labels, outcome summaries, analysis details, and participant counts all matter together. The available record documents a completed study and selected descriptive results, but leaves important inferential details unreported.

15. Limitations

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

Several trial-specific details needed to interpret the primary outcome are not reported in the registry record. Although the design is identified as crossover, the treatment sequence, period duration, washout arrangements, and methods for evaluating period or sequence effects are not described. The registry also does not identify who was masked under the triple-masking designation or explain how masking was maintained.

The record lists enrollment of 13, while the primary outcome summaries each use n=9. It does not explain participant flow, whether the same participants contributed to both conditions, why fewer participants appear in the summaries, or how missing endpoint values were handled. The analysis population is not reported. These omissions limit evaluation of possible selection effects and the precision of a within-participant comparison.

The endpoint summaries provide means and standard errors, but not individual observations, standard deviations, paired differences, confidence intervals, or an inferential test. The registry lists zero analyses. The statistical model, assumptions, and handling of the crossover structure are not reported. A trial-specific sample-size justification, statistical analysis plan, multiplicity strategy, and interim-analysis information are also not reported in the registry record.

The posted primary endpoint is a laboratory measure of plasma glutathione at a specified pre-exercise time point. The record does not give a clinically meaningful threshold for this measure. It lists five secondary outcomes, but does not report their results. Thus, the posted information cannot establish effects on the broader cardiorespiratory and physical-capacity aims described for the study.

Safety interpretation is also limited by the absence of adverse-event definitions, collection methods, observation period, and death counts. The small outcome and safety summaries provide a narrow account of the recorded data, not a full picture of the trial's conduct or findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of N-acetylcysteine on Cardiorespiratory Control in COPD Patients With Mild-to-moderate Airflow Obstruction — NCT02579772.
• Registry record last updated 2018-06-14; status last verified 2018-05.
• Results first posted 2018-06-14.
• 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.

19. Record Summary

NCT02579772 is a completed Phase 4 randomized, triple-masked crossover study sponsored by Queen's University. It enrolled 13 participants with chronic obstructive pulmonary disease and mild-to-moderate airflow obstruction. The interventions were N-acetylcysteine pills and placebo pills.

The primary endpoint was circulating plasma glutathione, measured in micromolar before exercise on day 4 of each experimental arm. The N-acetylcysteine summary was 8.97 with standard error 0.61 and n=9; the placebo summary was 7.05 with standard error 0.49 and n=9. The registry reports zero analyses and does not post an inferential treatment comparison.

Five secondary outcomes are listed. The record does not report their results, explain the difference between enrollment and endpoint summary counts, or describe the crossover analysis, missing-data handling, or sample-size justification. Safety summaries record zero serious adverse events in either condition and one other adverse event in the N-acetylcysteine condition versus zero in placebo; deaths are not reported in the registry record.