Effect of iNO on Invasively Derived Pulmonary Pressures in Patients With PAH: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of iNO on Invasively Derived Pulmonary Pressures in Patients With PAH (NCT02734953), a na phase 2 study. The primary outcome is Difference in Ambulatory 6 Minute Walk Distance (6MWD) Pulmonary Artery (PA) Pressures (Systolic, Diastolic, Mean) Between the Post-intervention (iNO+) and Pre-intervention (iNO-) Condition as Measured by the CardioMems Device.

2. Clinical Question

The clinical question is about a within-participant change in measured pressures, not a comparison between independently assigned treatment groups. The study summary places this question in the context of exercise: it describes pulmonary vascular resistance as potentially increasing with exercise in people with pulmonary vascular remodeling, and says the investigators intended to examine inhaled nitric oxide during standard exercise techniques. However, the primary outcome description focuses on pre- and post-intervention pulmonary artery pressure measurements. The record does not report the actual pressure values, the direction or size of any change, or an inferential analysis. It therefore establishes what was intended to be measured, but does not establish what the measurements showed.

3. Trial Design

The registry describes a completed phase 2, single-group study with an enrollment of 10. The intervention was inhaled nitric oxide. Allocation is listed as not applicable, masking as none, and the study model as single group. These features mean the registry does not describe a blinded, randomized comparison with a separate control group. Instead, the recorded primary comparison is between measurements before and after intervention in the same general study group.

Participants were described as having pulmonary arterial hypertension and as having separately and previously received an implanted CardioMems pulmonary artery monitoring device. The intervention description specifies inhaled nitric oxide at 0.075 mg/kg IBW/hr and assessment of pulmonary pressures by CardioMems before and after administration. The primary outcome description identifies baseline as t=0 and the post-intervention assessment as t=2h, with a timeframe of 2 hours. The summary also refers to standard exercise techniques, but the registry record does not report a detailed exercise protocol.

The primary outcome names systolic, diastolic, and mean pulmonary artery pressures and gives mmHg as the unit. Its title also includes “Ambulatory 6 Minute Walk Distance,” while the description specifies a difference in pressure between baseline and the post-intervention condition. The record lists change in 6 Minute Walk Distance as a secondary outcome as well. This wording makes the intended primary measure less straightforward to identify from the title alone.

The study is marked completed, but completion status does not supply outcome results. The registry record does not report participant flow, withdrawals, adherence, baseline characteristics, or an analysis of the pre/post measurements. It lists 12 outcome measures and 0 analyses. Thus, the design can be described from the planned measurement structure, but the record does not permit an assessment of the observed clinical data.

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: All enrolled participants were included,

Overall Study

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Difference in Ambulatory 6 Minute Walk Distance (6MWD) Pulmonary Artery (PA) Pressures (Systolic, Diastolic, Mean) Between the Post-intervention (iNO+) and Pre-intervention (iNO-) Condition as Measured by the CardioMems Device, measured over 2 hours.

The primary endpoint is described as the difference between baseline and post-intervention pulmonary artery pressures measured with the CardioMems device. It names systolic, diastolic, and mean pressure, gives mmHg as the unit, and identifies a 2-hour timeframe. A difference over time can describe whether measurements within a study group shifted after an intervention, while retaining the same pressure scale used by the device.

Pulmonary artery pressure is relevant to the study’s stated focus on pulmonary vascular parameters in pulmonary arterial hypertension. The study summary explains that the investigators were interested in pulmonary pressure responses in the setting of exercise and inhaled nitric oxide. The registry lists cardiac output, oxygen saturation, walking distance, dyspnea, oxygen requirements, mean arterial pressure, heart rate, and rate pressure product among the secondary outcomes. These measures provide additional physiological or functional context, but their listing does not establish that results were recorded or analyzed.

The endpoint wording needs careful reading. Its title includes ambulatory 6 Minute Walk Distance, yet the stated unit is mmHg and the description specifies pulmonary artery pressure differences. The record separately lists change in 6 Minute Walk Distance as a secondary outcome. Without clarification or posted outcome data, the registry does not resolve whether the title’s reference to walking distance was intended to define the primary endpoint or whether the pressure measures are the operative primary measures.

No baseline or post-intervention pressure values, change estimates, variability measures, or confidence intervals are reported in the registry record. Consequently, the endpoint definition can be described, but the magnitude and precision of the observed change cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In a pre/post study, measurements from the same participants are taken under different conditions or at different times. The intended comparison in this record is between pulmonary artery pressure at baseline and after inhaled nitric oxide. Because the measurements are linked within participants, a suitable analysis would generally account for that pairing rather than treating all pre-intervention and post-intervention measurements as if they came from unrelated people. This is a general statistical principle, not a description of an analysis reported for this study. The registry record lists 0 analyses and does not say what statistical method, if any, was used.

What does a change estimate represent?

A change estimate describes the observed difference between the measurements being compared, using the endpoint’s stated scale. For this endpoint, the scale is mmHg. The registry’s description identifies a difference between baseline and the post-intervention measurement, but it does not give the observed values or the direction of subtraction. Without those details, the change cannot be reconstructed or interpreted quantitatively. No calculation should be inferred from the endpoint title alone.

A point estimate, when reported, would summarize the observed change, while a confidence interval would express uncertainty around that estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision than a wider interval, but precision is not the same as clinical importance. The registry record does not report a point estimate or confidence interval for the primary outcome, so neither the estimated change nor its precision can be evaluated.

Why does the paired structure matter?

Repeated measurements on the same person are usually related. A paired approach uses that relationship in estimating change. In general, accounting for within-person pairing can distinguish the variability of individual changes from the variability across all measurements considered separately. The degree of pairing and the distribution of changes can affect uncertainty. The study’s single-group model and pre/post endpoint suggest a within-participant comparison, but the record does not report participant-level data or specify an analysis method. It is therefore not possible to confirm how the relationship between measurements was handled.

Measurement conditions also matter. The record describes CardioMems assessments before and after administration and refers to exercise techniques in the study summary. In general, timing, measurement repeatability, and conditions during assessment can influence repeated measurements. The registry does not provide enough procedural detail to assess those factors, and no observed measurements are posted.

How should the design affect causal interpretation?

Randomized control groups can help distinguish an intervention effect from changes that might occur for other reasons. This record lists allocation as not applicable, masking as none, and the model as single group. The comparison is therefore not a randomized contrast between separate groups. In general, a pre/post difference alone can reflect the intervention, but it can also be influenced by time, measurement variation, the exercise setting, or other changes around the assessment. These are general limitations of the design, not evidence that any particular factor altered the study’s measurements.

Masking can also matter when outcomes or procedures are susceptible to observer or participant expectations. The registry lists no masking. It does not report whether outcome assessment involved any safeguards against measurement or recording bias. This does not demonstrate that bias occurred; it means the available record does not permit an assessment of that possibility.

What can be learned from the planning assumptions?

The record describes a planning illustration based on the observed effect, using 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. Such calculations are planning illustrations, not observed power and not evidence that the study used a two-arm design. The registered study itself is described as single group. The record does not report the numerical planning outputs alongside the registry entries available for this analysis, and it does not report a trial-specific sample-size justification.

In general, a sample-size calculation depends on assumptions about the effect to detect, variability, allocation, and the chosen error rate. Changing those assumptions changes the resulting planning estimate. A planning illustration based on an observed effect is especially dependent on the reliability of that effect estimate. It should not be read as proof that the study was adequately powered, nor as a substitute for a confidence interval around the observed result. Since outcome estimates and variability are not reported, the precision of this study’s primary comparison cannot be judged.

Why is over-dispersion relevant in general?

For outcomes whose variability exceeds the assumptions of a chosen statistical model, standard errors and resulting uncertainty statements can be misleading if that extra variability is ignored. This issue is often described as over-dispersion. It is a general consideration when selecting models for outcomes with counts or other non-normal patterns; it is not reported as a feature of this trial. The primary endpoint is expressed as pressure in mmHg, and the registry record does not provide its distribution or the analysis used. There is no basis to claim that over-dispersion was present or that a particular model was required.

In short, the endpoint and study structure suggest a pre/post comparison, but the registry record does not report the analysis needed to evaluate the observed changes. Statistical interpretation would require the estimates, uncertainty measures, and enough methodological detail to understand how repeated measurements were handled.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary pressure outcome and secondary measures such as cardiac output, walking distance, oxygen saturation, dyspnea, oxygen requirements, mean arterial pressure, heart rate, and rate pressure product. When several outcomes are assessed, the chance of obtaining at least one apparently notable result can increase if many statistical tests are conducted without accounting for the number of comparisons. This is a general statistical concern, not a statement that such testing occurred in this study.

The registry record lists 0 analyses and does not report a multiplicity adjustment, a prespecified testing hierarchy, or which outcomes were analyzed. It is therefore not possible to determine how the multiple listed measures were handled, whether any were designated for formal inference, or whether results were selected for reporting. A list of outcome measures alone does not show that every measure was collected, analyzed, or tested.

The record also does not report missing-data counts, reasons for missing measurements, or the analysis population. It does not specify whether the primary comparison included every enrolled participant, only participants with paired measurements, or another defined group. Nor does it report how incomplete pre/post measurements would have been handled. These details are important because a paired change analysis generally depends on having linked measurements, and missingness can affect both the number of usable observations and the interpretation of the result.

Enrollment is 10, but that figure does not establish that all participants contributed complete outcome data. The registry record does not report participant flow or the number with evaluable primary endpoint measurements. Without those details, the analysis denominator and the potential influence of missing data cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 10 participants at risk for serious adverse events, with 0 affected. It also lists 10 participants at risk for other adverse events, with 0 affected. These are event-count entries in the registry record; they do not provide descriptions of monitoring procedures, follow-up completeness, event definitions, or the time period over which events were assessed.

The deaths field is not reported in the registry record. A missing entry should not be interpreted as a reported count of zero. The record also lists no serious adverse-event terms. This communicates that no terms are listed in that field, but does not provide enough detail to establish how adverse events were collected or whether all types of events were systematically assessed.

These figures are descriptive of what the registry reports, not a detailed comparison of safety between treatment groups. The study is single group, with no separate control arm listed, and the record does not provide comparative estimates. The absence of reported affected participants in these fields should therefore be read narrowly and should not be expanded into a conclusion about overall safety.

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

The registry record identifies a study of inhaled nitric oxide in people with pulmonary arterial hypertension who had a CardioMems device. It describes pulmonary pressure measurements before and after administration, with the post-intervention assessment set at 2 hours. The study is marked completed and has an enrollment of 10. These registry entries clarify the study’s scope and the intended measurement, but they do not state what happened to the measured pressures.

The primary outcome description names systolic, diastolic, and mean pulmonary artery pressures and gives mmHg as the unit. Yet the outcome title also refers to ambulatory 6 Minute Walk Distance, while the registry separately lists walking distance as a secondary outcome. That ambiguity should be kept in mind when describing the study’s primary question. The record does not resolve it with posted result details.

No numerical primary outcome results, confidence intervals, or statistical tests are reported in the registry record. Therefore, the available information cannot establish the direction or magnitude of a change, the precision of any estimate, or whether measurements varied consistently across participants. It also cannot support a conclusion about whether any observed change was attributable to inhaled nitric oxide rather than other influences in a single-group pre/post design.

The record lists secondary measures and adverse-event counts, but outcome listings do not demonstrate that results were analyzed. The serious and other adverse-event entries report 0 affected among 10 at risk for each category; the deaths field is not reported. Those entries do not amount to a complete account of safety or establish a comparison with a control group.

In general, a completed study and a defined endpoint are not the same as a reported result. Interpretation requires outcome estimates, uncertainty measures, analysis details, and information about who contributed data. Those elements are not reported in the registry record. The sound conclusion is limited: the registry describes a small single-group pre/post study and its intended measurements, while leaving the measured treatment-associated changes and their statistical uncertainty unreported.

13. Why This Trial Matters Statistically

This study is statistically notable because it uses a within-participant pre/post structure for a physiological measurement. Such designs can be useful for describing how measurements change across conditions in the same group, particularly when the question concerns a short-term response. Their interpretation nevertheless depends on clear endpoint definitions, consistent measurement conditions, and an analysis that respects the pairing of observations.

The registry makes the study structure visible: a single group, no masking, and a baseline-to-post-intervention pressure comparison. That structure also highlights why an observed pre/post difference, if reported, would not automatically isolate an intervention effect. Without a randomized comparison group, other influences over the measurement period cannot be distinguished as readily. This is a design consideration, not a claim that a particular alternative explanation occurred.

The endpoint wording illustrates a reporting issue with statistical consequences. The title combines ambulatory 6 Minute Walk Distance with pulmonary artery pressures, while the unit and description focus on pressure, and walking distance is also listed as secondary. Clear endpoint specification is important for deciding which estimate is primary, how multiplicity should be handled, and what result should guide interpretation.

The registry lists 12 outcome measures but 0 analyses, and it does not post primary outcome estimates or uncertainty intervals. As a result, the record can support discussion of design and reporting, but not evaluation of the study’s empirical pressure findings. This distinction is useful for clinical researchers: a registration record can define the intended question and outcomes, while the statistical conclusions require analyzable results and transparent methods.

The safety entries also show why counts need context. Zero affected participants are listed for serious and other adverse events, but detailed ascertainment information and a reported deaths value are absent. Statistical reading requires attention not only to the displayed counts, but also to what was measured, who was followed, and what the record leaves unreported.

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 primary limitation for interpreting the trial is the absence of reported efficacy results. The registry does not give baseline or post-intervention pulmonary pressures, participant-level changes, summary estimates, or measures of uncertainty. Consequently, the magnitude, direction, and precision of the primary outcome cannot be evaluated.

The study is a single-group, unmasked pre/post design, with allocation listed as not applicable. It does not provide a randomized control comparison. Even if a change estimate were available, the design alone would not distinguish intervention-associated change from other influences occurring around the assessment. The registry does not report procedural detail sufficient to evaluate those influences.

The endpoint description is not fully clear: its title refers to ambulatory walking distance as well as pulmonary artery pressures, while its unit and description specify pressure differences. Walking distance is also listed as a secondary outcome. The record does not resolve this discrepancy or identify a reported analysis that would clarify the intended primary measure.

The registry lists 12 outcome measures and 0 analyses, but does not state which outcomes were collected, how multiplicity was addressed, or what analysis populations were used. It does not report missing-data amounts, participant flow, or whether all enrolled participants had paired measurements. Details of the exercise protocol, measurement repeatability, and analysis methods are also not reported in the registry record.

The adverse-event fields list zero affected for serious and other events, but provide limited context; deaths are not reported in the registry record. These limitations mean the event entries cannot be treated as a complete safety assessment. Taken together, the record documents the planned question and broad design, but leaves key result and methodology information unavailable for independent statistical interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of iNO on Invasively Derived Pulmonary Pressures in Patients With PAH — NCT02734953.
• Registry record last updated 2018-09-24; status last verified 2018-08.
• Results first posted 2018-09-24.
• 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.

18. Record Summary

The registry describes a completed phase 2, single-group study of inhaled nitric oxide in pulmonary arterial hypertension, with an enrollment of 10. Participants were described as having a previously implanted CardioMems device. The intervention description specifies 0.075 mg/kg IBW/hr, and the primary outcome description compares pulmonary artery pressures at baseline and after 2 hours.

The primary outcome names systolic, diastolic, and mean pulmonary artery pressure in mmHg, although its title also mentions ambulatory 6 Minute Walk Distance. The record lists 12 outcome measures and 0 analyses. It does not report primary outcome estimates, uncertainty measures, missing-data details, or statistical methods. Serious and other adverse-event entries each list 0 affected among 10 at risk; the deaths field is not reported in the registry record. The available record describes the design and intended measurements, but does not report the measured primary results.