Oral Cyclosporine in Chronic Obstructive Pulmonary Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Cyclosporine in Chronic Obstructive Pulmonary Disease (NCT00974142), a randomized phase 1, phase 2 study. The primary outcome is Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blinded, placebo-controlled, parallel-group trial of oral cyclosporine in people with advanced-stage COPD. Its listed phases are PHASE1 and PHASE2, and its status is completed. The study’s stated purpose was to evaluate the safety and effectiveness of cyclosporine as a therapy for the adaptive immune response in advanced COPD. The posted primary outcome is specifically a safety measure: serum creatinine monitored for nephrotoxicity.

The primary outcome timeframe is 16 weeks. The description says serum creatinine was assessed at Week 2, 4, 6, 8, 10, 12 and 16. Measurements for each participant were averaged, and then the mean across participants was calculated. The outcome is reported as mean ± SD. The record does not report the cyclosporine dose, treatment schedule, or additional details about how blinding was maintained.

The registry enrollment field lists 43, while the brief summary says that a total of 30 subjects would be enrolled. These figures are not reconciled in the registry record. For the primary outcome, results are posted for 8 participants in the cyclosporine arm and 9 in the placebo arm. Those outcome-specific counts describe the posted summaries and should not be treated as a resolution of the differing enrollment figures.

The registry lists 14 outcome measures and 11 posted secondary outcomes. The named secondary measures include cyclosporine blood levels, several peripheral blood T-cell biomarkers, and a respiratory-function measure based on forced vital capacity. Detailed results for those secondary outcomes are not included in the registry record. The record does not report a protocol-level statistical analysis plan or explain how the primary outcome was intended to be compared between groups.

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: 772 patients underwent initial screening and 43 were eligible to sign consent. These patients underwent a second 2 week screening process and 17 subjects met all criteria for randomization

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 Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine, measured over 16 weeks.

The primary endpoint is serum creatinine, expressed in mg / dL, monitored over 16 weeks as a measure of nephrotoxicity. The registry describes measurements at Week 2, 4, 6, 8, 10, 12 and 16. For each participant, the values from the measurement occasions were averaged; the resulting participant-level means were then averaged across participants. The posted outcome is a group mean with a standard deviation.

Serum creatinine is used in this trial as a laboratory measure for monitoring kidney-related safety during cyclosporine treatment. That explains the endpoint’s role in the study, but the registry result is not itself a diagnosis of kidney injury. The posted group averages do not show each participant’s pattern over time, the range of values, or whether any individual met a clinical threshold. No threshold or definition of nephrotoxicity beyond monitoring serum creatinine is reported in the registry record.

The description refers to averaging repeated values within participants, but does not report how incomplete series were handled or how many scheduled measurements were available for each participant. It also does not state whether the endpoint was analyzed using the participant-level average as a single value or with another model. The posted summaries are 0.94 mg / dL with SD 0.2 for cyclosporine and 0.88 mg / dL with SD 0.2 for placebo. No confidence interval or formal between-group test is reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: serum creatinine is measured on a numeric scale and summarized by a mean. The registry reports each group’s mean and standard deviation, with participant-level averages formed from measurements over the 16-week interval. This is a descriptive summary rather than a complete comparison of the randomized groups. The record does not report a model, test statistic, confidence interval, or p-value for the primary outcome.

What does the mean describe?

The mean is the arithmetic average of the values being summarized. In this study’s endpoint description, measurements at Week 2, 4, 6, 8, 10, 12 and 16 were first averaged for each participant. The mean across participants was then calculated. Accordingly, the posted arm mean represents an average of participant-level summaries across the measurement period, not the mean at one particular visit. The registry does not report the participant-level values or the arm means at separate visits.

What does the standard deviation describe?

The standard deviation (SD) describes how dispersed values are around their mean. Here, the registry reports SD 0.2 in each arm. General statistical explanation: a larger SD indicates more variation among the observations being summarized, while a smaller SD indicates that values are more concentrated around the mean. SD is not a confidence interval and does not, by itself, indicate how precisely a group difference has been estimated. The registry does not state whether the SD calculation used a particular adjustment or provide further distributional summaries.

Why is a group comparison not available?

The record says the values are missing or not estimable for a two-arm comparison of this continuous endpoint, and it lists no posted analyses. The arm-level means and SDs remain descriptive information, but they do not constitute a reported test of the difference between groups. Without a reported contrast and its uncertainty, the registry does not show how compatible the observed summaries are with a range of possible underlying group differences.

General statistical explanation: a confidence interval for a contrast gives a range of values consistent with the data and the specified analysis, under that analysis’s assumptions. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the probability that the null hypothesis is true. Neither can be recovered as a reported result from this record. No new inferential statistic should be inferred from the two means and SDs when the registry states that a two-arm comparison was not estimable.

What role does randomization play?

Random allocation is intended to make treatment groups comparable at the start of a trial, on average, with respect to measured and unmeasured characteristics. Double blinding can reduce some forms of bias in treatment delivery, assessment, or reporting. These design features support a fair comparison when outcomes are analyzed as planned, but do not replace the need for a reported analysis. The registry does not describe the allocation sequence, concealment procedures, or how blinding was maintained.

General statistical explanation: a parallel-group trial assigns participants to one group and compares outcomes across groups rather than having each participant receive both interventions in sequence. This trial is identified as parallel. For a continuous outcome, an analysis might estimate a difference in means or use a model that accounts for relevant features of the data. Which approach was planned or used is not reported in the registry record.

Why can repeated measurements complicate analysis?

Repeated observations from the same participant are generally related, rather than independent. General statistical explanation: analysis methods for repeated measurements account for that within-person relationship, while a simple average reduces the series to one summary per participant. The registry describes averaging repeated creatinine readings for each participant, but does not say whether the primary group comparison, if any, used those participant-level means or another method. It also does not explain how the analysis addressed participants with incomplete visit data.

General statistical explanation: over-dispersion refers to variability greater than a statistical model expects. When present, it can make standard errors too small if the model does not accommodate the extra variation. This concept is not identified as an issue in the registry record, and no model details are posted that would allow assessment of whether over-dispersion was relevant to this endpoint.

How should planning estimates be read?

Any sample-size estimates associated with the results are planning illustrations based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Such estimates describe a hypothetical planning exercise under those assumptions. They are not observed power, do not demonstrate that the completed trial had a particular probability of finding an effect, and are not a substitute for a prespecified sample-size justification. The registry record does not report the trial’s own sample-size justification.

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("Cyclosporine", "Placebo")
n   <- c(8, 9)
m   <- c(0.94, 0.88)
sp  <- c(0.2, 0.2)
sd  <- sp      # posted standard deviations
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  Cyclosporine  8  0.940  0.200  0.773  1.107
CARM  Placebo  9  0.880  0.200  0.726  1.034

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 11 posted secondary outcomes. The named secondary outcomes span cyclosporine blood levels, peripheral blood T-cell biomarkers, and respiratory function. When a study evaluates multiple outcomes or multiple measures of related biological processes, there can be more opportunities for apparently notable findings by chance. General statistical explanation: multiplicity procedures can control the chance of false-positive conclusions across a defined family of tests, but the appropriate approach depends on the study’s prespecified questions and analysis plan.

The statistical plan for handling multiple outcomes is not reported in the registry record. The registry also lists no posted analyses for the primary continuous comparison, and the secondary outcome results are not described in the registry record for this analysis. It is therefore not possible to determine whether the outcomes were prioritized, whether any adjustment was intended, or how results across outcomes were to be interpreted together.

The primary endpoint description says measurements from several visits were averaged within each participant. The handling of missing visit measurements, incomplete participant-level series, withdrawals, or other missing data is not reported in the registry record. The record also does not identify the analysis population, such as whether the analysis was intended to include all randomized participants or a subset with available outcome measurements.

These omissions matter because the interpretation of a group summary depends partly on who contributed data and how missing observations were treated. They do not establish that data were missing or that an analysis was biased; they mean the registry record does not describe those aspects. The reported counts for the primary outcome and safety results should therefore be read as the counts attached to those posted results, not as a complete account of participant flow or analysis populations.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for each group using an at-risk count and an affected count. In the cyclosporine group, 0 of 8 at risk had a listed serious adverse event; in the placebo group, 0 of 9 at risk had a listed serious adverse event. Deaths are listed as 0 in both groups. The record gives no serious adverse-event terms among its top serious terms.

For other adverse events, the registry lists 6 of 8 at risk in the cyclosporine group and 5 of 9 at risk in the placebo group. These counts should not be confused with serious adverse events, which are reported separately. The registry does not provide event-specific details for these other adverse events in the registry record.

General statistical explanation: zero observed serious events does not establish that the underlying risk is zero. With relatively few participants represented in the posted safety results, an absence of observed events cannot rule out events that might occur in a larger group or over a different observation period. The record does not provide confidence intervals, a formal safety comparison, or definitions and follow-up details beyond the stated 16-week primary outcome timeframe. These counts are descriptive and do not establish equivalence between groups.

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

The result provides a limited descriptive account of serum creatinine during the 16-week treatment interval. The cyclosporine arm’s reported mean is 0.94 mg / dL with SD 0.2, and the placebo arm’s reported mean is 0.88 mg / dL with SD 0.2. The registry describes these as averages of measurements taken at scheduled visits, first summarized within participants and then across participants. The outcome-specific counts are 8 and 9.

Those summaries do not establish a treatment effect. The registry does not report a two-arm estimate, confidence interval, or p-value for the primary outcome, and it indicates that values were missing or not estimable for such a comparison. Consequently, the precision of a group contrast is unknown from the posted results. A descriptive difference between means is not, by itself, evidence of a reliable or clinically important difference.

The endpoint also has a focused meaning. Serum creatinine was monitored as a measure of nephrotoxicity; the result does not directly answer whether cyclosporine changes COPD symptoms, disease progression, or respiratory function. Although the registry lists respiratory function and immune biomarkers among secondary outcomes, those results are not described. The primary outcome should not be read as a comprehensive assessment of effectiveness.

The posted safety counts show no listed serious adverse events and no deaths in either arm, alongside other adverse events in both groups. Those observations describe the posted counts, not the full range of possible safety outcomes. The record does not provide enough detail to evaluate event severity, timing, or a comparative safety estimate.

Nor do the results establish that the groups were equivalent or that no effect exists. A null or unavailable inferential result is not proof of no difference. The registry’s different enrollment figures, its lack of a reported analysis population, and missing details on analysis methods further limit interpretation. The most defensible conclusion is that the registry posts group-level creatinine and adverse-event summaries, while leaving the comparative uncertainty and broader clinical implications unresolved.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between collecting repeated measurements and reporting a comparative result. The primary endpoint draws on serum creatinine measurements across a 16-week interval, with a participant-level average followed by a group mean. That approach gives a compact summary of repeated observations, but a group mean alone does not reveal how values changed over time or how uncertain a contrast between treatment groups might be.

The registry also illustrates why the unit of analysis and the analysis population matter. Repeated readings from one participant are not the same as independent observations from separate participants. The endpoint description makes clear that measurements were averaged within each participant, but the record does not explain how incomplete visit data were handled or how the final between-group analysis was intended to account for the repeated design. Those details are important for judging both the estimate and its uncertainty.

Another statistical issue is the difference between a safety endpoint and an efficacy question. Serum creatinine was selected to monitor nephrotoxicity, while the study’s stated purpose also concerns an adaptive immune response and effectiveness in advanced COPD. The registry names secondary biomarkers and respiratory function outcomes, but their detailed results are not presented in the registry record. Separate outcomes answer separate questions; a safety summary cannot stand in for evidence about respiratory benefit.

Finally, the registry record reports descriptive values but no estimable two-arm comparison for the primary continuous endpoint. This is a reminder that numerical results are not all equivalent in evidential content. Means and SDs describe the observed data, whereas a prespecified comparative analysis and uncertainty estimate would address how precisely the groups can be distinguished. Here, the posted summaries support description but leave the comparative inference unresolved.

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.

The registry record leaves important design and analysis details unclear. Its enrollment field lists 43, while the brief summary states that a total of 30 subjects would be enrolled. The record does not explain the difference. The primary outcome results include 8 participants in the cyclosporine arm and 9 in the placebo arm; the reasons these counts differ from the enrollment figures are not reported.

The primary endpoint is summarized over multiple visits, but the record does not report whether all scheduled measurements were available, how missing values were handled, or how many participants contributed a complete series. It also does not identify the analysis population or specify whether any participants were excluded from the primary summary. These gaps make it difficult to assess how representative the posted means are of the randomized groups.

The registry does not post an inferential comparison for the primary continuous endpoint. It gives no confidence interval, p-value, or model description, and states that values were missing or not estimable for a two-arm comparison. The record also does not report a statistical analysis plan, a sample-size justification, or how multiplicity across outcomes was addressed.

Further clinical details are limited. The dose and schedule of oral cyclosporine are not reported in the record, nor are detailed arm descriptions. The serum creatinine endpoint is identified as a nephrotoxicity measure, but a threshold for clinically important change is not provided. Safety results lack event-specific detail and uncertainty estimates. These limitations restrict interpretation of both the primary safety summary and the broader study aims; they do not, on their own, determine what the unreported data or analyses would show.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Oral Cyclosporine in Chronic Obstructive Pulmonary Disease — NCT00974142.
• Registry record last updated 2025-06-25; status last verified 2018-04.
• Results first posted 2018-05-09.
• 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

NCT00974142 is a completed randomized, double-blinded, placebo-controlled, parallel-group trial listed in PHASE1 and PHASE2. It evaluates oral cyclosporine A in advanced-stage COPD, with placebo as the comparator. The primary outcome is mean serum creatinine over 16 weeks, monitored as a measure of nephrotoxicity.

The posted primary summaries are 0.94 mg / dL with SD 0.2 for cyclosporine and 0.88 mg / dL with SD 0.2 for placebo. The corresponding outcome counts are 8 and 9. The registry does not post a two-arm inferential comparison, confidence interval, or p-value for this continuous endpoint. Serious adverse events and deaths are listed as 0 in both groups; other adverse events are listed for 6 of 8 and 5 of 9 at risk.

The registry lists 14 outcome measures and 11 posted secondary outcomes, but the primary comparative analysis, missing-data handling, analysis population, and multiplicity plan are not reported in the registry record. The results therefore provide descriptive summaries, not a precise estimate of a treatment-group contrast.