Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI (NCT03367312), a na phase 2 study. The primary outcome is Percent Change in Abnormal RBC Percentage.

2. Clinical Question

The study concerns pulmonary hypertension and asks whether MRI measurements of pulmonary gas exchange change after inhaled prostacyclin therapy. Participants were patients with pulmonary hypertension receiving a stable dose of inhaled prostacyclin. The MRI protocol included hyperpolarized 129Xe imaging and conventional proton MRI, with scans planned before treatment, immediately after treatment, and 2-4 hours after treatment. The primary outcome is the percent change in abnormal red blood cell percentage at 3 hours relative to baseline.

This is a within-group measurement question, not a comparison of prostacyclin with an untreated or alternative-treatment group. The registry record does not report a numerical result for the primary outcome, so the size and direction of any measured change cannot be described from the record.

3. Trial Design

This is a phase 2, completed, single-group study. The record lists enrollment of 11 and describes the study group as pulmonary hypertension patients on inhaled prostacyclin. The arm description says 10 subjects; the record does not explain the difference between that figure and the enrollment figure.

Allocation is listed as not applicable, and masking is listed as none. There is no randomized control group described. Accordingly, the design is suited to documenting imaging measurements around treatment in the study group, but it does not establish a randomized treatment contrast. Changes across measurement times would be within-group observations and could reflect treatment, measurement variation, or other time-related influences; the registry record does not specify a method to distinguish these possibilities.

The study seeks to use hyperpolarized 129Xe MRI to image ventilation and gas exchange, including three-dimensional images and spectroscopic measures of gas-exchange dynamics. Conventional proton MRI is also described, including a free-breathing ultra-short echo time scan intended to image lung structure. Scans are described as occurring before treatment, immediately afterward, and 2-4 hours afterward. The primary outcome is assessed at 3 hours.

The record lists a start date of 2018-03-29, primary completion on 2022-10-31, and a completed status. A detailed protocol, operational details for timing or measurement, and the statistical analysis plan are not reported in the registry record. The record also does not explain how many enrolled participants contributed data to the primary outcome.

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Same as participant flow information

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Abnormal RBC Percentage, measured over 3 hours.

The primary endpoint is percent change in abnormal red blood cell percentage, a measure described as reflecting pulmonary gas exchange. It is defined as 100 multiplied by the difference between the value at 3 hours and the baseline value, divided by the baseline value. The stated timeframe is 3 hours, and the outcome is summarized as a mean with standard deviation.

In general, a relative change expresses the difference from baseline in relation to the baseline measurement, rather than simply reporting the later value. Such a measure can be useful when the question concerns how a physiologic imaging index changes within participants. Its interpretation nevertheless depends on the baseline values, the measurement's variability, and how the imaging index is constructed. The registry record does not report those participant-level values or the numerical mean change.

The study rationale links 129Xe MRI to images of ventilation and gas exchange and describes spectroscopic indices for evaluating gas-exchange dynamics. The record does not provide a clinical threshold for the endpoint, identify a minimally important change, or explain how the endpoint would guide clinical decisions. Therefore, the endpoint should be read as an imaging-based physiologic measure, not as a direct measure of a clinical outcome.

The description gives the formula and timeframe, but the outcome estimate, standard deviation, confidence interval, and statistical test result are not reported in the registry record. Without those results, the magnitude, precision, and direction of the observed change cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary outcome summarized as a mean and standard deviation. It defines the outcome as percent change in abnormal red blood cell percentage from baseline to 3 hours. The formula compares the difference between the later and baseline values with the baseline value, then expresses that relative change as a percentage. The registry record does not report an estimated mean change or its standard deviation.

What does a mean summarize?

General statistical context: the mean is an average across the observations included in an analysis. For a change outcome, the mean would summarize the average participant-level change, provided the analysis first calculated change for each participant. A mean alone does not show whether observations cluster closely or whether some participants have substantially different changes. It also does not identify the pattern of individual results.

The standard deviation describes the spread of observations around the mean. It is not the same as the uncertainty in the mean: uncertainty in an estimated mean also depends on how many observations contribute and on the analysis. A confidence interval, when reported, gives a range of values compatible with the data and analysis under its assumptions. The registry record does not report a confidence interval for the primary outcome.

Why does the single-group design matter?

General statistical context: a pre-treatment and post-treatment comparison in the same participants uses paired observations. Pairing can account for the fact that measurements from the same person tend to be related. This is different from comparing independent groups, where observations come from different participants. However, a within-person comparison still does not supply the counterfactual measurement: what would have happened at the same time without the treatment. With no randomized comparator described, a change over time cannot be attributed uniquely to treatment using the registry record alone.

The outcome's percentage-change formula also depends on the baseline value. General statistical context: when baseline values are small or measured imprecisely, relative changes can be sensitive to baseline variation. Whether that issue is important for this endpoint cannot be assessed because the registry record does not report baseline values or participant-level measurements.

What is known about testing and uncertainty?

The record does not list an analysis or report a test statistic or p-value. It also does not identify a statistical model, adjustment variables, or a prespecified method for handling repeated measurements. General statistical context: a p-value is a measure of how compatible observed data are with a specified null model, given its assumptions; it is not a measure of effect size or clinical importance. A confidence interval addresses estimation uncertainty and should be interpreted alongside the estimate and design. Neither can be evaluated for this outcome from the registry record.

Over-dispersion is a concern in some count-data models when variability exceeds what the model expects. General statistical context: it can make standard errors and tests unreliable if ignored. The primary outcome in this record is described as a continuous measure, not a count outcome, and no count-model analysis is reported. There is no basis in the registry record to say that over-dispersion was assessed or relevant to the analysis actually used.

How should planning illustrations be read?

The record describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions for a hypothetical two-arm calculation, not the design of this single-group study. Such illustrations do not establish that the trial was adequately powered, and they are not observed power. The sample-size justification used for the actual study is not reported in the registry record.

Any calculation using an observed effect as its starting point inherits uncertainty from that estimate. General statistical context: a planning estimate can be unstable when based on limited data, and a smaller target effect requires a larger study under otherwise comparable assumptions. These concepts do not provide an estimate of this study's result. The registry record reports no primary outcome analysis from which the observed effect or its uncertainty can be assessed.

The registry record therefore permits explanation of the endpoint definition and broad design, but not verification of the analysis method. The number of participants contributing to the endpoint, handling of missing data, model assumptions, and statistical results 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("Pulmonary Hypertension Patients on Inhaled Prostac")
n   <- c(11)
m   <- c(-17.7)
sp  <- c(24.4)
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  Pulmonary Hypertension Patients on Inhaled Prostac  11  -17.700  24.400  -34.092  -1.308

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analyses. It does not report whether multiple imaging measures, timepoints, or secondary outcomes were tested as part of an inferential analysis, or whether any multiplicity adjustment was planned. A multiplicity strategy is therefore not reported in the registry record.

General statistical context: when many outcomes or comparisons are tested, the chance of finding at least one apparently unusual result can increase. Prespecifying a primary endpoint and an analysis hierarchy can help clarify which findings are confirmatory and which are exploratory. The record identifies the primary outcome, but does not report a statistical plan explaining how other imaging measures or timepoints were handled.

Missing-data procedures are not reported in the registry record. The record does not state whether all enrolled participants completed imaging, how missing scans or unusable measurements were handled, or whether an imputation method was used. The enrollment figure is 11, while the arm description refers to 10 subjects; the record does not explain the difference. The number contributing data to the primary outcome is not reported.

The analysis population is not reported in the registry record. There is no statement identifying whether the analysis included all enrolled participants, only participants with evaluable imaging, or another defined group. These omissions limit assessment of possible selection effects and the applicability of any estimate, even if an estimate were reported. No numerical primary outcome estimate is reported in the registry record.

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 adverse-event record lists 11 participants at risk for serious adverse events and 0 affected. It also lists 11 at risk for other adverse events and 0 affected, with 0 deaths. No top serious adverse-event terms are listed. These are the counts recorded for this study; they are not evidence that an event is impossible or that risk is absent.

General statistical context: an observed count is interpreted in relation to the number of people monitored, how events were defined, the duration and completeness of follow-up, and the method for collecting events. The registry record does not report detailed event definitions, monitoring procedures, or participant-level follow-up. It also does not report event rates or uncertainty estimates, and no rates should be inferred from the counts alone.

The record's adverse-event counts should be kept distinct from the primary imaging outcome. The primary endpoint concerns percent change in an imaging measure; the safety entries concern reported adverse events. The registry record does not provide additional information about severity categories beyond the serious and other adverse-event groupings or describe specific events.

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

The record establishes that a phase 2, single-group study was completed and that its primary question concerned change in an MRI-based gas-exchange measure after inhaled prostacyclin therapy. It defines the outcome and its 3-hour timeframe. It does not report the numerical primary result, so the record does not show whether the average value increased, decreased, or remained similar to baseline.

It also does not report an estimate of uncertainty around the outcome. Without a mean, standard deviation, or confidence interval, the precision of the measured change cannot be assessed. The absence of a reported result is not evidence that there was no change; it means the numerical outcome is not reported in the registry record.

The study has no randomized comparator described. General statistical context: an observed within-group change can be informative about measurements collected over time, but it cannot by itself establish what would have happened without treatment. The single-group design also does not provide a direct comparison with another treatment. Unmasked measurement may be vulnerable to observer or procedural influences, although the registry record does not describe whether or how such influences were assessed.

The endpoint is an imaging measure, rather than a clinical outcome such as symptoms or a health event. The registry record does not report a threshold for interpreting the change or evidence connecting a particular change to a patient-centered outcome. It therefore cannot support a claim about clinical benefit or lack of benefit. The safety entries record 0 serious adverse events, 0 other adverse events, and 0 deaths among 11 participants at risk in each listed event grouping; those counts should not be treated as proof of zero risk.

14. Why This Trial Matters Statistically

Statistically, the study illustrates the distinction between measuring a physiologic response and estimating a treatment effect. Serial MRI measurements can characterize ventilation and gas exchange in patients receiving inhaled prostacyclin. A single-group design, however, does not provide a randomized contrast against an untreated or alternative-treatment group. This distinction matters when interpreting any before-and-after change.

The endpoint is defined as percent change in abnormal red blood cell percentage at 3 hours relative to baseline. Explicitly defining the outcome and timeframe helps identify what the analysis is intended to estimate. Yet a definition alone is not a result: the registry record does not report the numerical estimate or its precision, so readers cannot judge the size or consistency of the measured response.

The study also combines hyperpolarized 129Xe MRI with conventional proton MRI. That imaging focus makes measurement quality and analysis choices important. General statistical context: repeat measurements from the same participant are related, and appropriate analyses should account for that dependence when estimating uncertainty. The statistical method used for this endpoint is not reported in the registry record.

The record's different enrollment descriptions also matter for interpretation: enrollment is listed as 11, while the arm description refers to 10 subjects. Without an explanation or an analysis population, the number contributing to the primary outcome is unclear. Together with the absence of numerical outcome results, this limits what can be concluded statistically from the registry record, regardless of the study's completed status.

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 principal limitation for statistical interpretation is that the registry record does not report a numerical result for the primary outcome. It gives the outcome definition and timeframe but no mean change, standard deviation, confidence interval, or test result. The effect's direction, magnitude, and precision therefore cannot be evaluated.

The single-group design has no randomized comparator described. Any change between baseline and later imaging would not by itself separate treatment-associated change from temporal effects, measurement variability, or other influences. The study is also listed as unmasked. The registry record does not describe safeguards against measurement or observer effects.

Enrollment is listed as 11, while the arm description refers to 10 subjects. The record does not reconcile these counts or state how many participants contributed to the primary outcome. It does not report participant-level missingness, exclusions, or the analysis population. These gaps prevent assessment of whether the analyzed group differs from the enrolled group.

The statistical analysis plan, model for repeated observations, handling of missing data, and multiplicity approach are not reported in the registry record. There is also no reported threshold for interpreting the imaging endpoint or explanation of its relationship to clinical outcomes. These limitations are specific to interpreting this study's posted information; they do not establish what analyses may have been performed outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI — NCT03367312.
• Registry record last updated 2023-10-18; status last verified 2023-10.
• Results first posted 2023-10-18.
• 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

NCT03367312 is a completed phase 2, single-group study titled “Assessing Response to Inhaled Prostacyclin With Hyperpolarized Xe MRI.” It concerns pulmonary hypertension patients receiving a stable dose of inhaled prostacyclin and evaluates hyperpolarized 129Xe and conventional proton MRI. The record lists enrollment of 11, while the arm description refers to 10 subjects.

The primary outcome is percent change in abnormal red blood cell percentage at 3 hours compared with baseline, summarized as a mean and standard deviation. No numerical primary outcome result or analysis is reported in the registry record. The design has no randomized comparator, and details of the statistical plan, missing-data handling, and analysis population are not reported in the registry record. The listed safety counts are 0 serious adverse events, 0 other adverse events, and 0 deaths.