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 A Study of Treprostinil to Treat Interstitial Lung Disease Pulmonary Hypertension (NCT05564637), a non-randomized phase 2 study. The primary outcome is Cardiac Output Reserve (Qc).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05564637 |
| Phase | Phase 2 |
| Condition | Pulmonary Arterial Hypertension, Interstitial Lung Disease, Healthy Adults |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mayo Clinic |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled people diagnosed with pulmonary arterial hypertension related to interstitial lung disease (PAH-ILD) and a separate group of healthy volunteers. The registry record reports total enrollment of 29. It also states that only 1 participant was enrolled in the healthy-volunteer arm and that results for that participant were withheld to protect privacy. The arm descriptions do not provide a complete account of participant characteristics.
Intervention
PAH-ILD patients received inhaled treprostinil and underwent right heart catheterization while exercising. An optional muscle biopsy was also part of that arm. Healthy volunteers underwent exercise right heart catheterization and could choose to have a muscle biopsy; they did not receive treprostinil according to the arm descriptions.
Comparator
The healthy-volunteer group offers a different population for physiological assessment, not a like-for-like control group for estimating a treprostinil effect in PAH-ILD. Allocation was non-randomized, and the groups therefore should not be interpreted as randomized treatment arms. The registry record does not describe a randomized or masked comparison.
Primary question
The primary endpoint was cardiac output reserve (Qc), defined as the difference between maximum cardiac output during exercise and resting cardiac output, measured by the direct Fick method in liters per minute. The stated purpose was to study exercise physiology in PAH-ILD and treprostinil's effects during exercise. The study summary also describes an interest in quality of life after 3 months of use. Numerical primary endpoint results are not reported in the registry record.
3. Trial Design
This was a phase 2, parallel, non-randomized study sponsored by Mayo Clinic. The registry record lists the study as completed, with a start date of 2023-03-13 and primary completion on 2024-10-30. Total enrollment was 29. The record describes two groups: healthy volunteers and patients with PAH-ILD. The PAH-ILD group received inhaled treprostinil; the healthy-volunteer group did not. Both groups underwent right heart catheterization while exercising, and muscle biopsy was optional.
The design does not support treating the healthy volunteers as a randomized control group. They were not assigned by randomization, and their health status differs from that of the PAH-ILD patients. Consequently, contrasts between these groups could reflect population differences as well as any differences related to treatment. The registry record does not describe a masked design; masking is listed as none.
The study summary states that the investigators sought to learn about treprostinil's effects during exercise and its effects on quality of life after 3 months. It also describes the study as examining mechanisms related to exercise limitations in PAH-ILD. The listed primary endpoint is cardiac output reserve at baseline, approximately 35 minutes. How that timeframe relates to individual procedures or other visits is not reported in the registry record.
The registry record lists ventilatory efficiency, NYHA functional class, and resting and exercise measures of pulmonary vascular resistance, pulmonary artery pressure, and right atrial pressure as secondary outcomes. It does not report a statistical analysis plan, a sample-size justification for the study's own design, or additional details about participant flow. The study's stated aims and design describe what was investigated; they do not establish an effect in the absence of reported numerical results.
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: 29 subjects were consented of which 5 screen failed prior to study group assignment.
Overall Study
| Stage | Healthy Volunteers | PAH-ILD Patients |
|---|---|---|
| STARTED | 1 | 23 |
| COMPLETED | 1 | 22 |
| NOT COMPLETED | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
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: Only 1 participant was enrolled in the healthy volunteers arm. Based on the low enrollment number in the healthy volunteers arm, no data is reported for the 1 subject in order to protect and maintain participant privacy/confidentiality.
| Characteristic | Unit | PAH-ILD Patients | Healthy Volunteers | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 0 | 23 | |
| Age, Continuous | years | 72.5 (SD 8) | — | 72.5 (SD 8) |
| Sex: Female, Male: Female | Participants | 10 | 0 | 10 |
| Sex: Female, Male: Male | Participants | 13 | 0 | 13 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 18 | 0 | 18 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 5 | 0 | 5 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 17 | 0 | 17 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 | 0 | 5 |
| Region of Enrollment: United States | participants | 23 | — | 23 |
6. Primary Endpoint
The registry lists the primary outcome as Cardiac Output Reserve (Qc), measured over Baseline, approximately 35 minutes.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Liters/Min |
| Endpoint classification | Continuous Endpoint |
Cardiac output reserve (Qc) describes the change from resting cardiac output to the heart's maximum output during exercise. The endpoint is defined as maximum exercise output minus resting output, measured by the direct Fick method and expressed in liters per minute. The registry record identifies the endpoint summary as a mean with standard deviation.
As a general statistical concept, an exercise reserve measure captures a response across two physiological states rather than describing only a resting value. It can therefore be used to characterize how cardiac output changes during exertion. That measurement rationale does not by itself establish that a difference is caused by treatment, particularly in a non-randomized study with a separate healthy-volunteer group.
The recorded timeframe is baseline, approximately 35 minutes. The precise timing and procedures underlying that label are not explained further in the registry record. The record states that results for the single healthy-volunteer participant were not reported to protect privacy. Numerical cardiac output reserve results for the PAH-ILD group are also not reported in the registry record. Without group estimates and their variability, the direction, size, and precision of any change in this endpoint cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies cardiac output reserve as the primary endpoint, but it does not report numerical endpoint results. There is therefore no posted mean, standard deviation, treatment-related change, confidence interval, or p-value for this endpoint to interpret. The stated aim and endpoint definition explain what the study sought to measure; they are not evidence of the size or direction of an observed effect.
The record gives a specific reason for withholding the healthy-volunteer result: only 1 participant was enrolled in that arm, and the data were not reported to maintain privacy and confidentiality. Numerical results for the PAH-ILD group are not reported either. The absence of those figures means readers cannot evaluate the observed cardiac output reserve values or their precision. It does not establish that the measurement was unchanged or that the study found no effect.
Interpretation of a between-group contrast would also require caution even if group values were available. Allocation was non-randomized, and healthy volunteers differ from patients with PAH-ILD. Such groups are not a like-for-like randomized comparison, so a contrast would not isolate a treatment effect. The registry record does not report an alternative adjusted analysis that would address this design limitation.
The registry lists nine outcome measures and zero analyses. It names secondary outcomes including ventilatory efficiency, NYHA functional class, and resting and exercise measures of pulmonary vascular resistance, pulmonary artery pressure, and right atrial pressure. Numerical results and analysis details for those outcomes are not reported in the registry record. Accordingly, the posted record does not permit assessment of the consistency of findings across outcomes, nor does it establish whether any observed changes were statistically distinguishable from chance.
As a general statistical concept, estimates are more informative when presented with measures of uncertainty, such as confidence intervals. A confidence interval describes the range of values reasonably compatible with the data under the chosen method; it does not eliminate design limitations or establish clinical importance. No such interval is reported for the primary endpoint in the registry record. The appropriate conclusion is therefore about reporting: the registry describes the endpoint and study design but does not provide enough numerical outcome information to estimate the primary result or its precision.
9. Statistical Methods Explained
What does a mean with a standard deviation describe?
The registry identifies the primary endpoint as a mean with standard deviation. In general, a mean describes the average measurement in a group, while the standard deviation describes how spread out individual measurements are around that average. These quantities answer different questions: the mean describes the group's central value, and the standard deviation describes variability among participants. Neither one alone is a measure of uncertainty in the estimated mean. The registry record does not report the numerical mean or standard deviation for the PAH-ILD group.
The endpoint is a continuous measure expressed in liters per minute. The record defines Qc as the difference between maximum cardiac output during exercise and resting cardiac output and says it was measured using the direct Fick method. The endpoint definition indicates how the value is formed, but the record does not include the individual or group values needed to examine its distribution or calculate an estimate of precision.
What can the study design establish?
The trial is listed as non-randomized, with no masking and a parallel model. In general, random assignment helps balance measured and unmeasured participant characteristics across treatment groups, on average. That protection is not available in a non-randomized comparison. Here, the healthy-volunteer and PAH-ILD groups also represent different populations, and only the PAH-ILD group received inhaled treprostinil. A difference between them could not be interpreted as a treatment effect without addressing those design features. No such adjusted analysis is reported in the registry record.
The design can describe measurements collected in each group, if results are reported, but the record does not provide numerical results for the primary endpoint. The presence of exercise right heart catheterization in both group descriptions does not make the groups comparable for estimating the effect of treatment. The healthy-volunteer result was withheld because there was only 1 participant in that arm.
What do confidence intervals and p-values contribute?
As general statistical concepts, a confidence interval gives a range of estimates compatible with the observed data under a specified statistical method, while a p-value summarizes how unusual the data would be under a stated null model. Neither quantity is a substitute for a meaningful effect estimate, and neither resolves bias from a non-randomized design. The registry record does not report a confidence interval, p-value, or numerical primary endpoint estimate. No inference about statistical significance can be drawn from the outcome description alone.
How should planning assumptions be understood?
The registry's sample-size assumptions describe 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. The stated effect to detect is a fraction of the observed effect. Such assumptions describe how a hypothetical planning calculation is framed; they are not the study's own sample-size justification. The record does not report that justification. Planning illustrations are not observed power and do not show whether a study detected an effect.
In general, power is a design-stage probability tied to an assumed effect, variability, sample size, and analysis method. A calculation based on an observed effect should not be treated as a retrospective measure of whether the study had a meaningful chance to detect a true effect. No numerical sample-size illustration or observed primary effect is reported in the registry record, so no such calculation can be evaluated from the posted results.
Why can over-dispersion matter?
As a general concept, over-dispersion occurs when observed variability is greater than a statistical model assumes. A model that understates variability can make uncertainty appear too small. The registry record does not identify an analysis model for the primary endpoint or provide data that would allow assessment of over-dispersion. It would therefore be inappropriate to infer that this issue occurred in this study; it is a general consideration when choosing methods for clinical data.
More broadly, the record does not describe the statistical model, covariate adjustment, handling of repeated measurements, or rules for exclusions. These details are not reported in the registry record. Without them, even a future reader of numerical summaries would have limited information about how the estimates were produced. The posted endpoint definition and design details support a description of the intended measurement, not reconstruction of an unreported analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome, cardiac output reserve, and secondary outcomes covering ventilatory efficiency, NYHA functional class, and resting and exercise pulmonary vascular resistance, pulmonary artery pressure, and right atrial pressure. It reports nine outcome measures and zero analyses. The statistical plan for evaluating multiple outcomes, including any adjustment for multiple comparisons or hierarchy among endpoints, is not reported in the registry record.
As a general statistical concept, when many outcomes are tested, the chance of at least one apparently notable result can increase if each is assessed independently without accounting for multiplicity. A prespecified hierarchy or adjustment can help clarify how evidence across outcomes should be interpreted. The listed outcomes alone do not reveal whether such procedures were planned or used. No conclusion about multiplicity handling can be drawn from the record.
Missing-data methods and the analysis populations are not reported in the registry record. The record does state that the healthy-volunteer primary endpoint result was withheld because only 1 participant was enrolled and disclosure could compromise privacy. This is a reporting and confidentiality explanation, not a description of how missing measurements were handled in the PAH-ILD group. The primary endpoint results for that group are not reported either.
The registry record does not explain whether all enrolled participants contributed to each outcome, how unavailable measurements were treated, or whether analyses followed a prespecified population definition. These omissions limit assessment of bias and reproducibility. They should not be filled in by assuming a conventional method; the record does not report one.
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 |
|---|---|---|---|
| Healthy Volunteers | 0 | 1 | 0.0% |
| PAH-ILD Patients | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Healthy Volunteers | 0 of 1 |
| PAH-ILD Patients | 0 of 23 |
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 |
|---|---|
| Healthy Volunteers | 0 of 1 |
| PAH-ILD Patients | 0 of 23 |
The registry lists serious and other adverse events for 1 healthy volunteer at risk and 23 PAH-ILD patients at risk. It reports zero participants affected by serious adverse events and zero affected by other adverse events in each group. Deaths are reported as zero in both groups, and no serious adverse-event terms are listed.
These figures are counts in the reported groups, not proof that adverse events are impossible or that no event could occur outside the recorded reporting period. As a general statistical consideration, small groups provide limited ability to characterize uncommon events. The registry record does not report the adverse-event collection period, event definitions, or additional details about ascertainment.
The safety counts should be kept separate from efficacy interpretation. They do not supply the missing cardiac output reserve results, and they do not establish the treatment's effect on exercise physiology or quality of life. The healthy-volunteer group and the PAH-ILD group also differ in role and treatment exposure, so their counts are not a randomized safety comparison. The posted figures describe the events recorded in the registry, with these limitations.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed phase 2 study examined inhaled treprostinil in PAH-ILD patients and included a separate healthy-volunteer group. It specifies cardiac output reserve as the primary endpoint, defines how that measure was formed, and describes exercise right heart catheterization and optional muscle biopsy procedures. It also lists several secondary physiological and functional outcomes.
What the record does not establish is the numerical result for cardiac output reserve. The primary endpoint estimate, its variability, and its uncertainty are not reported in the registry record. Numerical results for the PAH-ILD group are not reported; the single healthy-volunteer result was withheld for privacy. The listed outcomes and study aims cannot be used to infer whether cardiac output reserve increased, decreased, or remained similar.
The non-randomized design further limits causal interpretation. Healthy volunteers are not a like-for-like control for PAH-ILD patients, and the record does not describe a randomized treatment comparison or an adjusted analysis. Even if group values were available, comparisons would need to be interpreted in light of these differences and the analysis methods used.
As a general distinction, an endpoint's physiological relevance is separate from evidence that a treatment changes that endpoint, and a statistical estimate is separate from its clinical importance. The record does not provide enough outcome data to assess either the size or precision of an effect. It also does not report the specific quality-of-life measure or corresponding results, although the study summary mentions quality of life after 3 months of use. The most supportable reading is that the registry documents the study's question and design, while leaving its main numerical findings unavailable.
13. Why This Trial Matters Statistically
This study is statistically notable for the gap between a clearly defined physiological question and the limited outcome information available in the registry record. Cardiac output reserve is described as a continuous exercise-related measure, with a specified method of measurement and a mean-and-standard-deviation summary. Those details identify what an eventual result would represent. Without the numerical estimate and its variability, however, readers cannot assess the observed value or its precision.
The design also illustrates why group labels matter. A healthy-volunteer group can provide context for physiological measurements, but it is not a randomized control group for patients with PAH-ILD. Since allocation was non-randomized and only the PAH-ILD group received treprostinil, a contrast between groups would not isolate the treatment effect. Accurate statistical interpretation starts by respecting what the comparison can and cannot answer.
The record's privacy explanation for the healthy-volunteer result highlights a real tension between transparent reporting and confidentiality when a group is very small. At the same time, the absence of numerical results for the PAH-ILD group leaves the primary clinical question unresolved in the posted record. The listed secondary outcomes do not close that gap because their analyses and results are not reported.
These features make the study useful for understanding how endpoint definitions, comparison groups, reporting, and uncertainty shape interpretation. They also show why a completed study status should not be mistaken for a publicly interpretable result. The record describes a research program and the measurements it targeted; it does not provide enough numerical evidence to quantify the primary outcome.
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.
Important details needed to evaluate the primary endpoint are not reported in the registry record. These include the numerical PAH-ILD estimate, its standard deviation, and any confidence interval or inferential result. The healthy-volunteer result was withheld because the arm contained only 1 participant. The reason for that suppression is stated, but it does not provide a result for the PAH-ILD group.
The non-randomized design and distinct populations limit comparisons between the arms. The registry record does not describe random allocation, masking, or an adjusted analysis that would make the groups comparable for estimating a treatment effect. Total enrollment is 29, but the record does not provide a complete account of participant flow across outcomes or explain why the reported safety groups at risk include 1 healthy volunteer and 23 PAH-ILD patients.
The registry lists nine outcome measures and zero analyses, but outcome-specific numerical results and analysis methods are not reported. The statistical plan, missing-data procedures, analysis populations, and approach to multiple outcomes are also not reported in the registry record. The listed secondary outcome names do not specify all measurement details or provide results.
The study summary mentions quality of life after 3 months of use, but a specific quality-of-life instrument and numerical findings are not reported in the registry record. The primary endpoint timeframe is stated as baseline, approximately 35 minutes, without further explanation of the timing. These reporting limitations prevent a detailed assessment of the primary result, outcome consistency, and precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Treprostinil to Treat Interstitial Lung Disease Pulmonary Hypertension — NCT05564637.
- Registry record last updated 2025-12-03; status last verified 2025-11.
- Results first posted 2025-12-03.
- 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
The registry record describes a completed phase 2, parallel, non-randomized study sponsored by Mayo Clinic, with total enrollment of 29. PAH-ILD patients received inhaled treprostinil and underwent exercise right heart catheterization; an optional muscle biopsy was described. Healthy volunteers underwent exercise right heart catheterization and could have an optional biopsy.
The primary endpoint was cardiac output reserve, defined as maximum exercise cardiac output minus resting cardiac output and measured by the direct Fick method in liters per minute. Its timeframe is listed as baseline, approximately 35 minutes. Numerical primary endpoint results are not reported in the registry record. Results for the single healthy-volunteer participant were withheld for privacy. The record lists nine outcome measures and zero analyses.
Serious and other adverse events affected zero participants in each reported group, and deaths were zero in both groups. These safety counts do not replace the missing efficacy results. The non-randomized design and difference between the healthy-volunteer and PAH-ILD groups also preclude treating them as like-for-like randomized controls.