A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging (NCT04435782), a na phase 4 study. The primary outcome is Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI).

2. Clinical Question

The study was designed to assess changes in right ventricular function among participants with pulmonary arterial hypertension who received selexipag. Its primary question concerned change from baseline to Week 26 in right ventricular stroke volume, measured using pulmonary artery flow MRI. Because the study had a single group and no randomized comparator, it was not designed to estimate a treatment difference against a concurrent control group.

The clinical question is therefore about change over time within a treated group, not about a contrast between treatment and control. A before-and-after change can describe what happened to measured participants, but without a concurrent comparison group it cannot separate a treatment-associated change from other explanations such as the course of the condition, measurement variation, or changes in care. The registry record does not report a numerical answer for the primary question, so the direction, size, and precision of any observed change cannot be assessed from the posted results.

3. Trial Design

The study is listed as a prospective, multicenter, single-arm, open-label Phase 4 study of selexipag in pulmonary arterial hypertension. It began on 2021-07-07, had a primary completion date of 2023-07-28, and is marked terminated. Enrollment is listed as 9. The registry record does not state why the study was terminated.

In a single-arm design, participants receive the intervention without a concurrent group assigned to a different treatment or control. The planned primary assessment compared right ventricular stroke volume at baseline with its value at Week 26. The description therefore identifies a within-participant change as the main endpoint, rather than a between-group treatment contrast. Allocation is listed as not applicable, consistent with the single-group structure, and masking is listed as none. The study was open-label, so participants and study personnel were not masked to treatment assignment.

The listed intervention is JNJ-67896049, identified in the study summary as selexipag. Participants were to start at 200 mcg on Day 1. The dose was to be up-titrated from Day 1 through Week 12 (Day 84) to determine an individual maintenance dose. Participants were then to receive that maintenance dose from Week 13 to Week 52. The registry record describes this planned schedule; it does not report individual dose histories or adherence.

The registry lists 15 outcome measures, including MRI measures of right ventricular volume, ejection fraction, mass index, and global longitudinal strain, as well as functional class, NT-proBNP, and six-minute walk distance. These listed measures describe planned outcome coverage, not necessarily the availability of results for each measure. The record lists 0 analyses. That registry count does not establish whether analyses were or were not conducted outside the posted record. A detailed statistical analysis plan, including methods for handling multiple outcomes, is not reported in the registry record.

Because no control arm was included, the design can describe observed changes in participants who received the intervention but does not directly estimate what would have happened to comparable participants without it. The small enrollment also means that even a fully reported result would need to be read with attention to its uncertainty and the limited amount of information contributed by the cohort.

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:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, "N" (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and "n" (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the statistical analysis plan (SAP), participant wise data was collected and reported due to very limited number of participants enrolled.

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 Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI), measured over Baseline, Week 26.

The primary endpoint is change from baseline to Week 26 in right ventricular stroke volume (RVSV), assessed by pulmonary artery flow magnetic resonance imaging. Stroke volume is the amount of blood ejected by a ventricle with each heartbeat. In general, it is used as a measure of cardiac pumping function. In this study, the endpoint focuses on the right ventricle, which moves blood toward the lungs.

MRI provides an imaging-based way to assess cardiac structure and function. The registry specifies pulmonary artery flow MRI for the primary measure; it does not report further technical details about image acquisition, central reading, quality control, or how measurements were combined. The endpoint is expressed in milliliters and compares the Week 26 measure with baseline. A change score places the focus on within-participant movement over the stated follow-up interval, rather than the absolute value at a single assessment.

In general, a change endpoint can be useful when the scientific question concerns whether a measured feature shifts over time. Interpretation depends on the observed estimate, its variability, and the amount of missing information, as well as on the measurement process. A numerical change alone would not establish why the change occurred, particularly in an uncontrolled study. Here, the registry describes the endpoint and its time points but does not report the numerical change, its dispersion, or a confidence interval. The size and precision of the result therefore cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the estimand: the quantity a study is intended to describe or compare. The primary endpoint identifies a within-group change from baseline to Week 26 in right ventricular stroke volume, measured in milliliters by pulmonary artery flow MRI. It is not a treatment-versus-control difference because no control group is listed. The registry record does not report a detailed estimand, including how participants with missing Week 26 measurements were to be handled or which summary statistic was the primary target.

What does a change score represent?

In general, a change score compares each participant's follow-up measurement with that participant's baseline measurement, then summarizes those changes across the analysis population. The summary might use a mean or another statistic, but the exact method for this endpoint is not reported in the registry record. A change score can account for differences in starting values in a descriptive sense, but it does not remove the limitations of an uncontrolled design. It also depends on having measurements at the relevant time points or a stated method for handling missing measurements.

Change can be summarized in different ways, and those choices affect interpretation. A mean change is sensitive to unusually high or low participant changes; a median change emphasizes the middle observation. The registry primary-endpoint description identifies the outcome and timing but does not specify a summary measure or provide numerical results. No distributional information or participant-level values are reported, so readers cannot judge whether a summary would reflect a consistent pattern or be strongly influenced by individual observations.

How should precision be understood?

General explanation: an estimate is a numerical summary of the observed data, while a confidence interval expresses uncertainty around that estimate under a specified statistical model. A narrower interval generally indicates greater precision than a wider interval, although the interval's interpretation depends on the method and assumptions. The registry record does not report a primary-endpoint estimate or confidence interval, so precision cannot be assessed. It also does not report the dispersion measure needed to understand how much participant outcomes varied around a summary.

A p-value, when reported, addresses compatibility between observed data and a specified null model under the test's assumptions. It does not state the probability that a treatment works or establish causality. No primary-endpoint p-value or test method is reported in the registry record. In the absence of an estimate, interval, and test result, statistical significance cannot be evaluated, and statistical significance would not in itself resolve the lack of a control group.

Why does the single-arm structure matter?

General explanation: a randomized comparison is designed to estimate differences between groups while reducing systematic differences in treatment assignment. In a single-arm study, all participants receive the same listed intervention. A change from baseline may be clinically or scientifically descriptive, but it can reflect multiple influences besides treatment. These include natural variation over time, measurement variability, co-occurring care, and changes in participant circumstances. Without a concurrent comparison group, the study cannot directly estimate the counterfactual outcome that would have occurred in similar participants without the intervention.

Open-label status is another design feature. It means masking is listed as none. In general, knowledge of treatment can influence participant behavior, clinical decisions, or assessments that involve judgment. The primary endpoint uses MRI, but the registry record does not describe image-reader masking, central reading, or other safeguards, so no assumption about those procedures is warranted. The record also does not provide details that would allow assessment of whether open-label conduct affected measurement or follow-up.

What can planning calculations show?

Sample-size planning uses assumptions about an effect to estimate how many participants a future study might need under a chosen statistical design. General explanation: such calculations depend on the target effect, variability, type I error rate, power target, allocation, and the analysis model. A planning illustration based on an observed effect is not a result from the trial's original design and is not observed power. The registry record says that planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. Those assumptions are for illustration and do not describe the single-arm study's actual design. The registry record does not report the original sample-size justification or the protocol's planning assumptions.

Because the primary numerical result and its variability are not reported, the observed effect and uncertainty cannot be evaluated from the registry record. Any sample-size illustration that relies on an observed effect should not be mistaken for evidence that the actual study had a particular probability of detecting an effect. The record does not report an original target sample size, a sample-size justification, or the planned power for this study.

Why does over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. For count outcomes, it can make standard errors too small if the model's variability assumption is too restrictive. This study's primary endpoint is a continuous MRI measurement rather than a count outcome, so count-model over-dispersion is not the central issue for interpreting that endpoint. In general, however, outcome variability matters because it affects uncertainty around a summary. The registry does not provide a dispersion estimate for the primary MRI outcome, so the degree of participant-to-participant variability cannot be assessed.

For safety outcomes, counts and event categories require their own careful interpretation. The posted figures are descriptive counts in the treated group. The record does not provide a comparative risk estimate or a method-based uncertainty interval for those counts. With enrollment of 9, the number of observed events is limited, and an event count should not be read as a stable estimate of how often an event would occur in a broader population.

Finally, the registry lists 0 analyses. This should be read narrowly as the number of analyses listed in that record. It does not establish that no statistical work occurred, nor does it substitute for a full statistical analysis plan. Planned tests, covariate adjustment, handling of protocol deviations, and the exact analysis population for the primary endpoint are not reported in the registry record. The available information supports understanding the intended endpoint and design, but not reconstructing a complete analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary MRI measure and multiple secondary outcomes. When a study assesses several outcomes, the chance of at least one apparently unusual result can increase if each is tested independently without accounting for the number of tests. General explanation: multiplicity procedures can control this issue by adjusting significance thresholds, organizing outcomes into a hierarchy, or distinguishing primary from exploratory analyses. The registry record does not report whether multiplicity adjustments, a testing hierarchy, or other procedures were planned. The listed primary outcome is identifiable, but no numerical primary result or secondary outcome estimates are reported in the posted results.

Missing-data methods are also not reported in the registry record. The endpoint requires baseline and Week 26 measurements to characterize change, but the record does not state how participants without a measurement at either time point would be handled. It does not report imputation methods, a complete-case rule, sensitivity analyses, or the number evaluable for the primary outcome. These details matter because missing observations can affect both the analysis population and the interpretation of a change estimate.

The primary endpoint description refers to a safety analysis set that included all participants who received at least 1 dose of study intervention. It also distinguishes the overall number evaluable for an outcome from the number evaluable for specified rows. That description does not establish how many participants contributed to the primary MRI analysis. A complete accounting of participants assessed at baseline and Week 26 is not reported in the registry record.

The record lists 0 analyses. This is not sufficient to conclude that no analysis was performed. It means the registry record does not list analyses in that count. Details about analysis populations, protocol deviations, covariate adjustment, sensitivity analyses, interim analyses, and the prespecified statistical plan are not reported in the registry record. Without those details and the outcome estimates, readers cannot assess whether the posted result follows a specified analysis strategy or how robust it is to alternative assumptions.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure (11.1%), vaginal haemorrhage (11.1%).

The safety record lists the Selexipag group with 9 participants at risk for serious adverse events and 1 affected participant. For other adverse events, 9 participants were at risk and 9 were affected. The record lists 0 deaths. These are counts in the treated study group, not comparisons against another group, and the record does not establish that an event was caused by the intervention.

The serious adverse event terms listed are Cardiac Failure and Vaginal Haemorrhage, each reported as 11.1%. These percentages are presented as event-term listings. The registry information does not clarify whether the terms occurred in separate participants or whether one participant could contribute to more than one term. They should not be added together or treated as independent participant counts.

General explanation: adverse-event counts describe what was recorded during a specified study period; causal attribution requires more than observing that an event occurred after treatment began. Interpretation also depends on event definitions, timing, severity, follow-up, and the participants' underlying health. Those details are not fully available in the registry record. The small enrollment means these counts provide limited information about event frequency beyond the participants observed. They do not establish comparative risk or predict the experience of a larger population.

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

The registry record documents a prospective, multicenter, open-label, single-arm Phase 4 study of selexipag in pulmonary arterial hypertension, with an intended primary assessment of right ventricular stroke volume change from baseline to Week 26. It also lists an enrollment of 9, a dosing schedule extending through Week 52, and selected safety counts. Those details describe the study's structure and the information posted in the record.

The record does not report a numerical primary-endpoint result, its variability, a confidence interval, or a p-value. Therefore, it does not show how much RVSV changed, which direction the change took, or how precisely it was estimated. The absence of a posted estimate is not evidence that there was no change, and it is not evidence that a change occurred. It leaves the primary outcome's observed result unavailable for statistical interpretation.

Even a complete within-group change estimate would have limits. Because the study had no randomized comparator, a change over time could not be attributed to the intervention alone. A single-arm before-and-after comparison cannot distinguish treatment-associated change from natural history, measurement variation, or other influences. The open-label design and lack of reported measurement-process details add uncertainty about how assessment procedures were conducted.

The study's enrollment and safety counts are also descriptive. They do not provide a controlled estimate of efficacy or comparative safety. The registry's serious adverse event listings and other adverse-event counts should not be read as proof of causation, and the lack of a listed death count does not characterize every aspect of safety.

In general, a registry record is most informative when it presents outcome estimates alongside analysis populations, uncertainty measures, and methods for missing data and multiplicity. Those details are not reported for the primary result in this record. The appropriate conclusion is limited: the study was intended to measure a specified MRI change in a small, treated group, but the numerical result and its precision cannot be assessed from the posted registry information. This record alone does not support a causal treatment conclusion.

13. Why This Trial Matters Statistically

This study is statistically notable because it asks a focused physiological question using an imaging-based endpoint, while its design is a single-arm before-and-after study. That pairing makes the distinction between measurement and causal inference especially important. MRI can quantify a cardiac feature, but a precise measurement method does not by itself create a controlled comparison. The endpoint's numerical result, measurement variability, and analysis details are necessary to judge what the observed change means; the registry record does not report those results.

The small enrollment of 9 also highlights the difference between conducting a study and obtaining a precise estimate. General explanation: a small cohort may be informative for feasibility or descriptive purposes, but estimates can be sensitive to individual observations and may have substantial uncertainty. Without a numerical estimate and interval, readers cannot quantify that uncertainty in this study. The record does not state whether feasibility was an objective or provide a sample-size justification, so neither should be inferred.

The registry lists a range of secondary measures, including MRI parameters, functional class, NT-proBNP, and six-minute walk distance. A broad set of outcomes can describe different aspects of a condition, but it also raises questions about how the analysis plan prioritized results and handled multiple comparisons. Those methods are not reported in the registry record. The outcome list alone does not show which measures have results or how they were analyzed.

Finally, the record demonstrates why completeness matters in registry reporting. Design details and safety counts are useful, but they cannot substitute for a primary estimate, precision measure, and transparent analysis population. With no posted primary numerical result, readers cannot evaluate the magnitude of the endpoint change. With no comparator, they also cannot interpret a within-group change as a treatment effect. The statistical importance of the record lies in understanding these boundaries, rather than drawing a conclusion that the available results do not establish.

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.

Several limitations specific to this trial shape interpretation. It was a single-arm study, with no concurrent control group and no randomized comparison. Its open-label status means masking is listed as none. A change from baseline can be described, but a causal contrast cannot be estimated directly from this design. The registry record does not report safeguards such as masked MRI reading, so their use cannot be assumed.

Enrollment was 9, which limits the amount of information available for estimating the distribution of outcomes or uncommon safety events. The registry record does not report the number of participants with evaluable primary MRI measurements at baseline and Week 26. As a result, the relationship between enrollment and the primary-endpoint analysis population cannot be assessed from the posted record.

The primary endpoint is specified, but its numerical result, dispersion, and uncertainty interval are not reported in the registry record. The registry count of 0 analyses likewise does not provide an analysis plan or establish that no analysis took place. Details about outcome summaries, missing data, multiplicity, protocol deviations, and sensitivity analyses are not reported. The primary endpoint description is truncated after referring to a prespecified matter, so that incomplete text cannot be used to infer additional methods.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record lists a planned dose-titration schedule through Week 12 and maintenance dosing through Week 52, but it does not provide participant-level exposure or adherence. Although safety counts and serious event terms are present, the entries do not establish causality or comparative risk. These limitations mean that the posted record supports a description of the intended study and selected observations, but not a full assessment of efficacy, precision, or the reasons the study ended.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging — NCT04435782.
• Registry record last updated 2025-03-30; status last verified 2025-03.
• Results first posted 2024-08-20.
• 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

NCT04435782 is listed as a prospective, multicenter, single-arm, open-label, Phase 4 study of selexipag in pulmonary arterial hypertension. Enrollment was 9, and the study status is terminated. The listed intervention is JNJ-67896049, with planned dose titration through Week 12 and maintenance dosing through Week 52.

The primary endpoint was change from baseline to Week 26 in right ventricular stroke volume measured by pulmonary artery flow MRI. The registry record does not report a numerical primary-endpoint result or its precision. It lists 15 outcome measures and 0 analyses. The safety record lists 1 participant with a serious adverse event, 9 with other adverse events, and 0 deaths. These safety entries are descriptive and do not establish causality. The reason for termination and the detailed statistical analysis plan are not reported in the registry record.