Optimizing and Standardizing 129Xe Gas Exchange MRI to Visualize Regional Therapy Response in Interstitial Lung Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimizing and Standardizing 129Xe Gas Exchange MRI to Visualize Regional Therapy Response in Interstitial Lung Disease (NCT04855305), a non-randomized phase 2 study. The primary outcome is Thoracic Cavity Volume Measured in Liters.

2. Clinical Question

3. Trial Design

This completed Phase 2 study enrolled 47 participants and is described as multi-centered and NIH-sponsored. The listed condition is interstitial lung diseases. Its stated purpose is to develop an optimal protocol for noninvasive 129Xe gas exchange MRI to detect changing disease activity in interstitial lung diseases. The record lists hyperpolarized 129Xe as the intervention.

The design is non-randomized, unmasked, and parallel. It lists patients with interstitial lung disease and healthy volunteers as the two groups. Because allocation was not randomized, the groups should not be treated as equivalent by design. Any difference between them could reflect group characteristics as well as the condition under study. The record does not report a planned adjustment strategy for such differences. The group descriptions do not provide additional details about participant eligibility, imaging visits, or treatment history.

The study start date is 2021-11-12, and the primary completion date is 2025-06-11. Its status is completed. The primary endpoint is thoracic cavity volume in liters, reported as a mean and standard deviation, at 1 day, immediately after administration of hyperpolarized 129 Xenon. The registry record lists 5 outcome measures and 5 analyses, but further details about those measures and analyses are not reported in the registry record. Results for the primary endpoint and a statistical comparison between groups are also not reported in the registry record.

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 Thoracic Cavity Volume Measured in Liters, measured over 1 day (immediately after administration of hyperpolarized 129 Xenon).

Thoracic cavity volume is a continuous measure expressed in liters. The primary endpoint is specified as a mean with a standard deviation, at 1 day, immediately after administration of hyperpolarized 129 Xenon. This describes the quantity the study planned to summarize and the time at which it was assessed. The registry record does not report the observed mean or standard deviation.

In general, a volume measure can provide a quantitative description of the anatomy captured during imaging. In a study whose stated aim is to optimize and standardize 129Xe gas exchange MRI, a clearly defined measurement and assessment time can help make imaging results more interpretable across participants and sites. That general rationale does not establish that thoracic cavity volume is a direct measure of disease activity, nor does it show that the measurement detects a response. The registry record does not report validation results or explain how this endpoint is expected to relate to changing disease activity.

The endpoint is a measurement, not by itself evidence of a treatment effect. No endpoint result, uncertainty interval, or inferential test is reported in the registry record. The endpoint therefore identifies what was measured, but the posted information does not show its observed distribution or whether it differed between the listed groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is a continuous measurement, thoracic cavity volume in liters, summarized using a mean and standard deviation. In general, the mean describes the center of a set of measurements, while the standard deviation describes how spread out individual measurements are around that center. These quantities answer different questions: a mean gives a typical value for the group, while the standard deviation conveys variation among participants. Neither quantity alone indicates how precisely the mean has been estimated.

Precision is often described with a confidence interval. In general, a confidence interval gives a range of values compatible with the data and the statistical procedure used, reflecting sampling uncertainty. A narrow interval indicates greater precision than a wide interval, all else equal. The registry record does not report a confidence interval, mean, or standard deviation for the primary endpoint, so neither the endpoint's central value nor its precision can be assessed from the record.

Why does the allocation design matter?

Allocation is non-randomized, and the listed groups are patients with interstitial lung disease and healthy volunteers. In a randomized study, assignment is designed to reduce systematic differences between groups. In a non-randomized study, the groups can differ in participant characteristics that also relate to an imaging measurement. As a general statistical concern, such differences can complicate interpretation of a group contrast: an observed association may not be attributable solely to disease status.

The parallel model means the record identifies separate groups rather than a crossover sequence. No masking is listed. The registry record does not report an adjustment strategy, matching procedure, or a detailed analysis plan. Without those details and the endpoint results, it is not possible to determine how the analysis accounted for differences between groups or to evaluate the robustness of any comparison.

What can a significance test tell a reader?

In general, a statistical test evaluates how compatible observed data are with a specified null hypothesis under the assumptions of the test. A p-value is not the probability that a hypothesis is true, and it does not describe the size or clinical importance of an effect. An effect estimate and its uncertainty are needed to understand magnitude and precision. No test result or effect estimate for the primary endpoint is reported in the registry record.

The record mentions a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes planning for stated fractions of the observed effect. Such calculations are planning illustrations, not evidence that the study had a particular probability of detecting an effect after completion. They are not observed power. The registry record does not report the observed effect or the numerical outputs of those planning calculations, so no planning count can be interpreted from the available record.

Why can variation affect an analysis?

In general, the spread of measurements influences how precisely a group mean or difference can be estimated. Greater variation makes it harder to distinguish a group contrast from random variation, especially when the available sample is limited. A standard deviation is one way to describe this spread for a continuous outcome. If the distribution is unusually skewed or contains influential observations, the mean and standard deviation may not fully convey its shape. The registry record does not report the endpoint distribution or diagnostic checks, so those features cannot be assessed.

Over-dispersion is a general concern for some kinds of outcomes when observed variability exceeds what a statistical model assumes. It matters because standard errors and confidence intervals can be too small if the model understates variation. The primary endpoint is continuous volume, but the registry record does not state the model used or indicate whether over-dispersion was assessed. This general concern should not be mistaken for evidence that over-dispersion occurred in this study.

What information is needed to interpret results?

For a complete statistical reading, it is useful to know the group-specific endpoint summaries, the number of participants analyzed, the estimated contrast if one was planned, and its uncertainty. It is also useful to know the model, any covariates, assumptions, handling of missing values, and the analysis population. These details help distinguish the observed data from model-based estimates and clarify what comparisons the results support. The registry record does not report these details for the primary endpoint.

The study lists 5 outcome measures and 5 analyses. In general, testing multiple outcomes or contrasts raises a multiplicity question: when many hypotheses are assessed, the chance of at least one apparently unusual result can increase if no adjustment or interpretation strategy is used. Whether that issue applies, and how it was handled, is not reported in the registry record. The count of outcomes and analyses alone does not reveal which tests were confirmatory or whether an adjustment was used.

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("Patients With Interstitial Lung Disease", "Healthy Volunteers")
n   <- c(4, 41)
m   <- c(2.8, 3.43)
sp  <- c(0.664, 0.639)
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  Patients With Interstitial Lung Disease  4  2.800  0.664  1.743  3.857
CARM  Healthy Volunteers  41  3.430  0.639  3.228  3.632

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures and 5 analyses. It identifies thoracic cavity volume as the primary endpoint, but does not describe the other measures or analyses in enough detail to establish which statistical questions were tested. Whether multiplicity was addressed, and by what method, is not reported in the registry record.

In general, when several outcomes or comparisons are tested, the chance of obtaining at least one apparently notable result can increase. A prespecified primary endpoint and a clear hierarchy of secondary questions can help readers understand how results should be interpreted. The record identifies a primary endpoint, but does not report an analysis hierarchy or multiplicity procedure. No inference about whether adjustment was necessary or applied can be made from the outcome and analysis counts alone.

Missing-data methods and the number of participants with evaluable primary endpoint measurements are not reported in the registry record. In general, missingness can affect a result if the participants without measurements differ systematically from those with measurements. The approach to incomplete scans, unusable measurements, or other missing observations can therefore matter, but such details are not reported.

The analysis populations are also not reported in the registry record. The total enrollment of 47 does not establish how many participants were included in each endpoint analysis or whether all enrolled participants were analyzed. These omissions limit assessment of attrition, selection, and the population to which any result might apply.

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 0% reporting threshold.

The safety listing records 0 serious adverse events, 0 other adverse events, and 0 deaths among 4 patients with interstitial lung disease at risk. For 42 healthy volunteers at risk, it also records 0 serious adverse events, 0 other adverse events, and 0 deaths. These figures describe the events recorded for the listed groups; they do not provide detail about event definitions, collection procedures, or the duration of safety observation.

In general, seeing no recorded events in a group does not establish that the underlying risk is zero. The amount of information about uncommon events depends on the number observed and the number of participants followed, as well as the duration and completeness of event monitoring. The registry record does not report follow-up duration for safety or additional details about ascertainment. The group sizes in this safety listing should not be treated as the analysis sample sizes for the primary endpoint.

The study's primary question concerns MRI protocol development and a continuous imaging measure. The safety counts are a separate description and do not provide evidence about the measurement's performance or its relationship to disease activity.

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

The registry record describes a completed Phase 2, multi-centered study focused on optimizing and standardizing noninvasive 129Xe gas exchange MRI for interstitial lung diseases. It identifies hyperpolarized 129Xe as the intervention and thoracic cavity volume as the primary endpoint. The endpoint is specified in liters as a mean with standard deviation, assessed 1 day immediately after administration of hyperpolarized 129 Xenon.

Those details define the study's focus, but the registry record does not report the primary endpoint values, a group contrast, or a confidence interval. It therefore does not show the magnitude or precision of any observed difference in thoracic cavity volume. It also does not establish whether the MRI protocol detected changing disease activity. The stated purpose is to develop an optimal protocol; that purpose should not be confused with a reported demonstration of measurement performance.

The non-randomized design also limits causal interpretation of any group comparison. In general, patients with interstitial lung disease and healthy volunteers may differ in ways beyond the condition of interest. A comparison between these categories, even if numerically reported, would not by itself show that disease status caused a difference in the measure. The registry record does not report a strategy for addressing potential group differences.

The safety listing reports no serious adverse events, other adverse events, or deaths in either listed group. These counts are limited to the recorded groups and do not establish the absence of risk. Finally, the record's enrollment and completion status do not substitute for endpoint results. The available information supports a description of the study design and measurement, not a conclusion about treatment benefit, disease monitoring performance, or the clinical usefulness of the technique.

14. Why This Trial Matters Statistically

This study is statistically relevant because it centers on developing and standardizing a measurement rather than comparing randomized treatments. For imaging research, a clearly specified measurement, unit, and assessment time are important: they indicate what is being quantified and when. The registry record identifies thoracic cavity volume in liters and an assessment immediately after administration of hyperpolarized 129 Xenon. That definition gives readers a starting point for understanding the intended endpoint.

Protocol optimization and standardization raise general questions about reproducibility and comparability. If measurement procedures vary across sites or participants, observed variation may reflect the procedure as well as differences in the underlying biology. A standardized approach can, in principle, make measurements easier to compare. However, the registry record does not report reliability results, validation evidence, or the details of the optimization process. The stated aim should therefore be distinguished from evidence that standardization was achieved.

The non-randomized design is another important statistical feature. The listed groups are patients with interstitial lung disease and healthy volunteers, not randomized arms. In general, differences between such groups can reflect characteristics beyond disease status. This makes clear reporting of group summaries, analysis methods, and uncertainty especially valuable. Those primary endpoint results are not reported in the registry record.

The registry lists 5 outcome measures and 5 analyses, which makes transparent reporting of the analysis plan and multiplicity handling relevant to interpretation. The record does not report those details. Taken together, the study provides a defined measurement question and a protocol-development objective, while the posted results do not provide the quantitative evidence needed to assess endpoint behavior or measurement performance.

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 limitations constrain interpretation of the registry record. First, it does not report the primary endpoint mean, standard deviation, or a statistical comparison. This prevents assessment of the observed thoracic cavity volume values and their precision. No confidence interval or p-value for the endpoint is reported in the registry record.

Second, allocation was non-randomized, and the two listed groups are patients with interstitial lung disease and healthy volunteers. The record does not report group characteristics or an adjustment strategy. As a result, it is not possible to assess whether differences in participant characteristics could complicate a group comparison.

Third, the record's stated objective is protocol development, but it does not report the technical details needed to evaluate protocol optimization, reproducibility, or validation. The relationship between thoracic cavity volume and changing disease activity is not described in the endpoint information. The record therefore does not establish that the primary measure detects disease change.

Finally, the registry record does not report the analysis populations, endpoint-specific sample sizes, missing-data methods, full statistical model, or multiplicity approach. The listed enrollment of 47 and the safety group counts do not resolve these gaps. These limitations apply to interpretation of the registry record; they do not establish what analyses may have been performed outside the information reported in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Optimizing and Standardizing 129Xe Gas Exchange MRI to Visualize Regional Therapy Response in Interstitial Lung Disease — NCT04855305.
• Registry record last updated 2026-08-05; status last verified 2026-07.
• Results first posted 2026-08-05.
• 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

The registry record describes a completed Phase 2, non-randomized, unmasked, parallel study of hyperpolarized 129Xe in patients with interstitial lung disease and healthy volunteers. It reports enrollment of 47 and a study objective of developing an optimal protocol for noninvasive 129Xe gas exchange MRI. The primary endpoint is thoracic cavity volume in liters, summarized as a mean and standard deviation, at 1 day immediately after administration.

Numerical results for that endpoint and a group comparison are not reported in the registry record. The record lists 5 outcome measures and 5 analyses, but details about additional measures, analysis methods, missing data, and multiplicity are not reported. The safety listing records no serious adverse events, other adverse events, or deaths in either listed group. The registry record establishes the study's design and measurement focus, but does not provide the quantitative results needed to assess MRI measurement performance or disease-activity detection.