This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD) (NCT03473340), a randomized phase 2 study. The primary outcome is Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03473340 |
| Phase | Phase 2 |
| Condition | Disorder Related to Lung Transplantation, Chronic Lung Allograft Dysfunction |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan |
| Results posted | Yes |
2. Clinical Question
Population
Lung transplant recipients with chronic lung allograft dysfunction (CLAD) were the intended study population. The registry describes baseline measurements from all participants, while post-treatment percentage measurements were taken only from participants who completed the study. It does not report additional eligibility details in the record.
Intervention
The active intervention was oral pirfenidone capsules, given on a step-up schedule: 267 mg three times daily on Days 1 through 7, 534 mg three times daily on Days 8 through 14, and 801 mg three times daily from Day 15 through the end of treatment at 24 weeks.
Comparator
The comparator was placebo capsules. The registry lists the same oral capsule dosing schedule for placebo as for pirfenidone. The study was randomized, double-blinded, and used a parallel-group design.
Primary question
The primary question was whether pirfenidone, compared with placebo, would stabilize progression of functional small airways disease (fSAD) over 24 weeks. The outcome was change in the percentage of fSAD, assessed using parametric response mapping of inspiratory and expiratory high-resolution computed tomography images. The record does not report the numerical primary-outcome results or a statistical comparison between the groups.
3. Trial Design
STOP-CLAD is described as a phase two, randomized, double-blind, placebo-controlled, parallel-group study sponsored by the University of Michigan. The registry lists an enrollment of 24 and identifies the study status as terminated. It gives a start date of 2018-04-27 and a primary completion date of 2021-07-23. The reason for termination is not reported in the registry record.
The study compared oral pirfenidone capsules with placebo capsules. Both arms have the same listed step-up schedule, reaching 801 mg three times daily from Day 15 through the end of treatment at 24 weeks. The parallel design means participants were assigned to one arm rather than crossing between treatments, while double masking was intended to keep treatment assignment concealed from participants and relevant study personnel. The record does not report details about how randomization or masking was implemented.
The primary outcome concerned change in percentage of fSAD from baseline to 24 weeks. The record describes imaging-based assessment using inspiratory and expiratory high-resolution computed tomography images that were co-registered for parametric response mapping. Secondary outcomes included change in forced expiratory volume in one second (FEV1), change in forced vital capacity (FVC), adverse events related to study treatment, and treatment intolerance.
The registry lists five outcome measures and five analyses, but the primary outcome has several categories or time points and is not reduced to one comparison in the posted results. Numerical primary-outcome estimates, uncertainty intervals, and a test result are not reported in the registry record. The reason for stopping the study and the details of any statistical analysis plan are also not reported.
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
| Stage | Pirfenidone Capsule | Placebo Capsule |
|---|---|---|
| STARTED | 13 | 11 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 5 | 2 |
Reasons for not completing this period:
| Reason | Pirfenidone Capsule | Placebo Capsule |
|---|---|---|
| Follow up not possible due to COVID restrictions | 3 | 0 |
| Withdrawal by Subject | 1 | 0 |
| Lost to Follow-up | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Baseline measures taken from all participants. Post treatment percentage measurements taken only from participants who completed the 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.
| Characteristic | Unit | Pirfenidone Capsule | Placebo Capsule | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 11 | 24 | |
| Age, Continuous | years | 59.6 (SD 11.6) | 57.5 (SD 13.5) | 58.6 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 10 | 2 | 12 |
| Sex: Female, Male: Male | Participants | 3 | 9 | 12 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 11 | 24 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 12 | 11 | 23 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 13 | 11 | 24 |
| Lung Function FEV 1, FVC,: FEV1 | liters | 1.400769 (SD 0.5887057) | 1.410909 (SD 0.4713906) | 1.41 (SD 0.527) |
| Lung Function FEV 1, FVC,: FVC | liters | 2.544615 (SD 0.8378904) | 2.517273 (SD 0.7226353) | 2.53 (SD 0.77) |
| CLAD Phenotype: FEV1 First Decline | Participants | 5 | 4 | 9 |
| CLAD Phenotype: Concurrent FEV1 and FVC Decline | Participants | 8 | 7 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping, measured over Baseline, 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of change of fsad |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in the percentage of functional small airways disease (fSAD), measured by parametric response mapping. fSAD is the functional imaging measure named in the registry; the study’s stated aim was to assess whether its progression could be stabilized during treatment. The endpoint was assessed at baseline and 24 weeks using inspiratory and expiratory high-resolution computed tomography images that were co-registered. The registry describes the outcome as a mean, with standard deviation as its measure of dispersion.
An imaging measure can characterize aspects of lung structure and function that may not be captured by a single conventional spirometry measure. In this study, fSAD was selected to assess small-airway disease progression in lung transplant recipients with CLAD. The registry also lists FEV1 and FVC as secondary outcomes, so the imaging endpoint was part of a broader assessment rather than the only measure of lung function.
The record’s population description is important for interpreting change: baseline measures were taken from all participants, whereas post-treatment percentage measurements were taken only from participants who completed the study. Thus, the available endpoint at follow-up may reflect a subset of the enrolled population. The record does not report the group means, standard deviations, the number with observed follow-up measurements, or a between-group estimate for the primary endpoint. Without those results, the direction and precision of the primary comparison cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the question and outcome but does not report the numerical primary-outcome comparison. It therefore does not establish, from the posted results, how much fSAD changed in either arm, how different the changes were between arms, or how precisely that difference was estimated. The outcome title and objective describe what the study set out to assess; they are not evidence of the result. No conclusion about the treatment effect on fSAD can be drawn from the record’s primary-outcome information alone.
The endpoint is a continuous measure reported as a mean with standard deviation. In general, a mean describes the center of a group’s observed values, while a standard deviation describes their spread. For a treatment comparison, the difference between group means would describe the estimated contrast on the measurement scale. A confidence interval would show the range of effect sizes compatible with the data and analysis, subject to the assumptions used. Neither group means nor a confidence interval for the primary comparison is reported in the registry record.
The registry describes baseline measurements from all participants but post-treatment measurements only from study completers. This distinction matters because a change from baseline requires observations at both time points, and the people with follow-up data may differ from those without it. If completion is related to outcome or treatment experience, a completer-only result may not represent the outcomes that would have been observed for everyone randomized. The record does not report the number of participants with primary-outcome follow-up by arm or an analysis addressing missing measurements.
The study was terminated, but the reason is not reported in the registry record. Termination alone does not reveal whether it arose from recruitment, operational, safety, or other considerations. Nor does it indicate the direction or size of any treatment effect. The record does not state whether a planned analysis was completed, whether there were interim analyses, or why the posted primary outcome was not reduced to one comparison.
Safety information is available, but it should be read separately from the missing primary efficacy comparison. The registry lists serious adverse-event counts of 0 for pirfenidone and 4 for placebo, with no deaths recorded in either arm. The counts are descriptive and do not, by themselves, establish a treatment-related difference. The record also lists other adverse events and serious-event terms, but does not provide enough information to attribute individual events to treatment or to make a precise comparative safety estimate.
Overall, the registry record documents a randomized comparison of pirfenidone and placebo and describes how the primary imaging outcome was intended to be measured. It does not provide the primary group results needed to judge the estimated effect or its precision. The distinction between study objective, outcome measurement, and observed comparative result is essential: the first two are described, while the third is not reported in the registry record.
9. Statistical Methods Explained
The registry describes a continuous primary outcome, expressed as the mean change in percentage of fSAD and accompanied by standard deviation. It does not report the numerical results or the statistical method used for the primary comparison. General explanations below clarify how such statistics are commonly interpreted; they should not be read as a description of an analysis that the registry confirms was performed.
What does a mean represent?
For a continuous outcome, the mean is the arithmetic center of the observed measurements. A mean change summarizes the average change among the observations included in a particular group and analysis. In a randomized trial, the treatment question generally concerns the contrast between the change in the intervention group and the change in the comparator group. That contrast is more informative about a comparative effect than looking at one group’s change in isolation, because change can occur in both groups for reasons unrelated to the assigned treatment.
The registry says baseline measures came from all participants and post-treatment percentage measurements came only from participants who completed the study. The record does not state how change was calculated for participants without a post-treatment measurement, or whether any model used information from incomplete records. Consequently, the precise population represented by a change estimate would depend on the analysis approach and available observations, which are not reported.
Why report a standard deviation?
A standard deviation describes how dispersed observed values are around their mean. It is not the same as the uncertainty in the estimated mean or in a difference between groups. A wide spread among individual measurements can coexist with a more precise estimate when the analysis contains substantial information, while a smaller spread does not by itself guarantee a precise treatment comparison. Precision also depends on the amount of usable data and the analysis design. The registry lists standard deviation as the dispersion measure but does not give its values for the primary outcome.
What would a confidence interval add?
In general, a confidence interval expresses the statistical uncertainty around an estimated effect. Its width reflects how precisely the effect is estimated under the chosen analysis and assumptions. A narrow interval indicates greater precision than a wide interval, but it does not establish that the measurement is clinically important. The interval’s position relative to no difference can help describe compatibility with that possibility, but interpretation also depends on the outcome scale, analysis plan, and study context. No confidence interval for the primary comparison is reported in the registry record.
What can a significance test say?
A significance test evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. A small p-value can accompany a modest estimate, while a larger p-value can reflect limited precision. A test result cannot replace the effect estimate and its uncertainty. The registry record does not report a primary-outcome test statistic or p-value.
Why does randomization matter?
Random assignment is intended to make the groups comparable, on average, with respect to factors that could affect the outcome. This supports a causal comparison when the trial’s conduct and analysis preserve the benefits of randomization. Randomization does not guarantee that the groups are identical, particularly in a small study, and it does not resolve problems caused by missing outcomes or deviations from assigned treatment. The registry identifies the allocation as randomized but does not report the method of sequence generation, concealment, adherence, or the analysis population used.
How should planning calculations be read?
Sample-size illustrations are planning exercises, not observed evidence about the treatment effect. The record describes an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it specifies that the effect to detect is a stated fraction of the observed effect. Such calculations depend on assumptions about the effect size and analysis and are not a measure of the probability that the trial’s findings are correct. They are also not observed power. The registry does not report its own design justification or state that these planning assumptions were used to design the trial.
In general, power is a design concept tied to an assumed effect and statistical model. It is not a property that can be recovered as a definitive measure of evidence after results are observed. Planning for a smaller fraction of an observed effect would represent a different assumed target; it would not change the trial’s observed data. Since the primary comparison itself is not reported, the registry’s planning illustration cannot substitute for the missing effect estimate and its uncertainty.
What does over-dispersion mean?
Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small and uncertainty intervals too narrow. The primary endpoint is described as continuous, and no model or evidence of over-dispersion is reported in the registry record. This concept therefore explains a general statistical issue rather than a demonstrated feature of this trial’s analysis.
The registry lists five analyses, but it does not provide a complete statistical analysis plan or enough detail to identify the methods used for each outcome. The primary result is not presented as one comparison because it has several categories or time points. Without the estimates, analysis specification, missing-data approach, and uncertainty measures, readers cannot independently evaluate the primary treatment contrast from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and five analyses. The primary outcome includes several categories or time points and is not reduced to one comparison in the posted results. The statistical analysis plan, including any prespecified hierarchy of outcomes or adjustments for multiple comparisons, is not reported in the registry record.
Multiplicity arises when several hypotheses or comparisons are assessed. In general, the more opportunities there are to identify a statistically unusual result, the more important it is to understand which comparisons were planned and how their interpretation was controlled. This does not mean that every analysis must be adjusted in the same way; the appropriate approach depends on the trial’s aims and prespecified analysis plan. The record does not provide enough detail to determine whether or how multiplicity was addressed.
Missing outcome data are also relevant. The registry states that baseline measures were taken from all participants, while post-treatment percentage measurements were taken only from participants who completed the study. It does not report the number of participants with follow-up measurements by arm, the reasons for missing measurements, or an analysis of how missingness may affect the primary comparison. It also does not report whether the analysis included all randomized participants or only those with available measurements.
In general, complete-case analysis can be biased if completion is related to treatment assignment or outcome. Other approaches may use assumptions or models to address incomplete data, but the registry record does not identify any such method. The difference between baseline and follow-up populations therefore limits interpretation of any unreported change estimate and prevents assessment of how well it represents the randomized groups.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pirfenidone Capsule | 0 | 13 | 0.0% |
| Placebo Capsule | 4 | 11 | 36.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pirfenidone Capsule | 0 of 13 |
| Placebo Capsule | 0 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pirfenidone Capsule | 11 of 13 |
| Placebo Capsule | 9 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Pirfenidone Capsule | Placebo Capsule |
|---|---|---|---|
| Respiratory infection | Infections and infestations | 0 of 13 | 2 of 11 |
| C. difficile colitis | Infections and infestations | 0 of 13 | 1 of 11 |
| Urinary tract infection | Infections and infestations | 0 of 13 | 1 of 11 |
| Hyponatremia | Metabolism and nutrition disorders | 0 of 13 | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pirfenidone Capsule | Placebo Capsule |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 13 | 2 of 11 |
| Diarrhea | Gastrointestinal disorders | 4 of 13 | 3 of 11 |
| Gastroesophageal reflux disease | Gastrointestinal disorders | 3 of 13 | 0 of 11 |
| Gastrointestinal upset | Gastrointestinal disorders | 2 of 13 | 1 of 11 |
| Respiratory infection | Infections and infestations | 1 of 13 | 2 of 11 |
| Respiratory congestion | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 2 of 11 |
| Fatigue | General disorders | 1 of 13 | 1 of 11 |
| Headache | General disorders | 2 of 13 | 0 of 11 |
| Myalgias | General disorders | 1 of 13 | 1 of 11 |
| Belching | Gastrointestinal disorders | 1 of 13 | 1 of 11 |
Serious events with the highest arm-level rate: respiratory infection (18.2%), c. difficile colitis (9.1%), urinary tract infection (9.1%), hyponatremia (9.1%).
The registry reports serious adverse-event counts of 0 in the pirfenidone arm and 4 in the placebo arm. It records no deaths in either arm. These are descriptive counts in a small trial; they do not establish that treatment caused or prevented an event, and they do not by themselves quantify the uncertainty around a comparative safety difference. The registry does not report a statistical comparison of serious adverse events.
For other adverse events, the registry lists 11 in the pirfenidone arm and 9 in the placebo arm, with 13 and 11 at risk, respectively. These figures should be read as registry entries, not as a complete account of event timing, severity, duration, or relationship to study treatment. The record does not provide those details in the information.
The listed serious-event terms include respiratory infection at 18.2%, C. difficile colitis at 9.1%, urinary tract infection at 9.1%, and hyponatremia at 9.1%. The registry does not specify the denominators or arm-specific attribution for these percentages in the record. They should not be added together or interpreted as mutually exclusive categories. Safety comparisons are descriptive, and the counts do not establish a treatment effect.
12. What the Result Does, and Does Not, Mean
This trial record matters because it documents a randomized, double-blind comparison of pirfenidone with placebo for CLAD and specifies an imaging-based primary outcome. The study was designed to examine whether treatment might stabilize progression of fSAD over 24 weeks, using parametric response mapping of high-resolution computed tomography images. The registry also identifies lung-function and safety outcomes that complement the primary imaging measure.
What the record does not establish is the result of the main comparison. No numerical primary-outcome estimates, confidence interval, or statistical test result is reported. The study objective is not the same as a finding: stating that investigators examined whether fSAD could be stabilized does not show whether the observed data supported that possibility, or how precisely any effect was estimated.
The registry’s description of follow-up also affects interpretation. Baseline measurements were taken from all participants, but post-treatment percentage measurements were taken only from participants who completed the study. Without the number of observations by arm, the reasons for incomplete follow-up, and the missing-data method, it is not possible to determine how representative the endpoint data were of the randomized groups.
Likewise, the listed serious adverse-event counts are not a causal comparison. They describe what was recorded, but do not by themselves show whether treatment caused a difference in risk. The record does not give a complete account of event-level details or a statistical safety analysis.
The status of terminated is part of the study record, but the reason is not reported. It cannot be used on its own to infer whether the study stopped because of safety, feasibility, recruitment, or a treatment result. In short, the record describes the design, outcome measurement, and some safety counts; it does not report enough primary-outcome information to determine the estimated treatment effect or its precision.
13. Why This Trial Matters Statistically
Clinical trials of imaging-based outcomes raise statistical questions that are relevant beyond this study. The selected measure must be defined clearly, collected consistently, and interpreted on a scale that readers can understand. Here, the registry identifies percentage of fSAD measured by parametric response mapping and describes the use of co-registered inspiratory and expiratory high-resolution computed tomography images. That precision in outcome definition is useful, but it cannot replace the reporting of group estimates and their uncertainty.
Randomized trials are most informative when they report the comparison between assigned groups, not only separate descriptions of each group. A treatment contrast, together with an uncertainty interval, helps distinguish the estimated size of an effect from the variability in the data. In this record, the primary comparison is not presented as one result because the outcome has several categories or time points. This makes clear reporting of the chosen analysis especially important, yet the analysis details are not reported.
Completion-based follow-up is another statistical concern. When post-treatment measurements are available only for participants who complete a study, the composition of the analyzed group may differ from the randomized population. Clear reporting of the amount and reasons for missing data, along with the analysis approach, is necessary for judging whether estimates could be affected by incomplete follow-up. Those details are not reported for the primary endpoint.
The safety entries also illustrate why event counts need context. Counts are useful for describing what was recorded, but small studies generally provide limited precision for comparing uncommon outcomes. The counts should be interpreted alongside denominators, event definitions, attribution, and uncertainty, rather than as proof of a treatment-related difference. The registry provides some counts and event terms but not a full comparative safety analysis.
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 principal limitation for interpretation is the absence of numerical results for the primary outcome. The record identifies the measure and assessment window but does not report the mean change by arm, a between-group estimate, a measure of uncertainty, or a primary-outcome test result. The treatment effect and its precision therefore cannot be assessed from the registry record.
The endpoint population is incompletely described. Baseline measurements were taken from all participants, while post-treatment percentage measurements were taken only from participants who completed the study. The record does not state how many participants completed follow-up in each arm, why participants did not complete the study, or how missing measurements were handled. This prevents evaluation of potential selection bias due to incomplete follow-up.
The study is listed as terminated, but the reason is not reported in the registry record. The record also does not describe the randomization procedure, concealment of allocation, masking implementation, adherence, protocol deviations, or analysis population. It does not provide a full statistical analysis plan, including how multiple categories or time points in the primary outcome were handled.
The safety information is limited to counts and listed serious-event terms. The registry record does not provide full event descriptions, timing, treatment attribution, or a statistical comparison. As a result, the counts are not sufficient to establish a comparative safety effect. These limitations are specific to the information recorded and should not be mistaken for evidence that an unreported procedure or analysis did or did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Studying the Treatment Effect of Pirfenidone in Chronic Lung Allograft Dysfunction (STOP-CLAD) — NCT03473340.
- Registry record last updated 2022-08-17; status last verified 2022-07.
- Results first posted 2022-08-17.
- 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.
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18. Record Summary
NCT03473340 is a University of Michigan phase two randomized, double-blind, parallel-group, placebo-controlled study of pirfenidone for chronic lung allograft dysfunction. The registry lists enrollment of 24, status as terminated, a start date of 2018-04-27, and a primary completion date of 2021-07-23. The reason for termination is not reported in the registry record.
The primary outcome was change in percentage of fSAD from baseline to 24 weeks, measured by parametric response mapping of inspiratory and expiratory high-resolution computed tomography images. Baseline measurements were taken from all participants; post-treatment percentage measurements were taken only from participants who completed the study. The numerical primary results and statistical comparison are not reported in the registry record.
The record also lists FEV1, FVC, treatment-related adverse events, and treatment intolerance as secondary outcomes. Serious adverse-event counts were 0 for pirfenidone and 4 for placebo, and no deaths were recorded in either arm. These safety figures are descriptive and do not establish a causal treatment difference.