Epoprostenol for Injection in Patients With Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Epoprostenol for Injection in Patients With Pulmonary Arterial Hypertension (NCT01470144), a na phase 3 study. The primary outcome is Treatment-emergent Adverse Events.

2. Clinical Question

The central statistical question is therefore descriptive: what adverse-event information does the registry report for the treated group, and how much can that information establish about safety in this extension? Because all patients belonged to the treatment group and the design had no control group, event counts describe what was recorded during participation. They cannot show how often the same events would have occurred in the absence of treatment or under a different treatment.

The study was an extension, not a stand-alone comparison of treatment strategies. This context matters: entry followed a preceding study, and the registry describes a purpose of continuing treatment after participation in that study ended. The results therefore relate to the extension population and its recorded follow-up; they should not automatically be generalized to all people with pulmonary arterial hypertension or to people who did not enter the extension.

3. Trial Design

The registry identifies this as a Phase 3, completed study of Epoprostenol in patients with pulmonary arterial hypertension. Its official title describes an open-label extension of Study AC-066A301 investigating the safety and tolerability of ACT-385781A. The brief description says the extension would assess safety and tolerability while providing a means to continue treatment after ending participation in AC-066A301.

The design is open-label, nonrandomized, and single-group. Allocation is listed as not applicable, and masking is listed as none. There is one treatment arm, described as single arm and open-label. These features mean that the registry does not offer a randomized comparison or a blinded assessment against a control group. Results must be read as observations in people receiving the study treatment, not as estimated treatment differences.

The registry reports enrollment of 41. The recorded study start is 2011-06-01, primary completion is 2015-06-01, and status is completed. The primary outcome timeframe is described as “On average 2.72 years.” That wording describes the endpoint timeframe but does not give a distribution of individual follow-up durations or establish that every patient was observed for the same period. Exposure Duration is listed as a secondary outcome.

For the primary endpoint, the registry identifies the population as all patients who received at least one dose of EFI. It does not report further details about the relationship between that population and the enrolled group, or the handling of patients with incomplete follow-up. The record lists two outcome measures and zero analyses. A statistical analysis plan, interim-analysis details, and sample-size justification are not reported in the registry record. The planning assumptions associated with illustrative sample-size calculations are not evidence of the study’s original design or of observed power.

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: All patients who received at least one dose of EFI

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 Treatment-emergent Adverse Events, measured over On average 2.72 years.

The primary endpoint is titled “Treatment-emergent Adverse Events.” Its unit is the number of patients, and the registry describes the timeframe as an average of 2.72 years. In general, a patient-count endpoint indicates how many people experienced an event during the specified observation period; it is different from counting every occurrence, since one person may experience more than one event. The endpoint title alone does not specify which event definitions, grading rules, or attribution procedures were used.

Safety and tolerability endpoints are used to describe unwanted events observed during treatment and follow-up. In an extension study, such information can characterize the experience recorded among continuing participants over the stated timeframe. The measure is descriptive in this single-group design: without a concurrent comparator, it cannot distinguish events associated with treatment from events that might also occur because of the underlying condition, other care, or background risks.

The primary endpoint is specified, but the registry record does not report its numerical result. The serious and other adverse-event counts reported elsewhere in the record are safety information, but they do not fill in the missing primary-endpoint result unless the record explicitly identifies them as that endpoint. The registry does not provide such a linkage or report an endpoint estimate with an uncertainty interval. Accordingly, the primary endpoint’s observed number of patients cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study estimates or describes outcomes among people who received the study treatment. The registry identifies this study as nonrandomized, open-label, and single-group, with no masking. As a result, there is no randomized control group to provide a concurrent reference for outcome rates. A count in the treatment group is an observation, not a treatment contrast. It can describe what was recorded in the study, but it cannot by itself show what would have happened to the same participants under another treatment or without the study treatment.

This distinction is especially important for safety outcomes. Some events may relate to treatment, some may relate to the underlying condition or other care, and some may occur for reasons not specified in the record. A controlled design can help assess differences between groups when its design and analysis support that comparison. This extension does not have such a group, so causal attribution cannot be recovered from the reported counts alone.

What is the difference between a patient count and an event count?

In general, a patient-count measure records how many people experienced an event at least once under the applicable definition. An event count can include repeated occurrences in the same person. These measures answer different questions: the first concerns the number of affected people, while the second concerns the volume of events. The primary endpoint is specified in terms of the number of patients. The adverse-event entries also give at-risk and affected patient counts. The record does not explain whether repeated events, event severity, timing, or recurrence were handled in a particular way.

A denominator gives context for a count, but it does not on its own communicate uncertainty or establish causation. Here, the safety entries identify patients at risk and patients affected in the treatment group. The record does not supply an inferential comparison or an uncertainty interval for these counts. It is therefore appropriate to describe the figures as reported counts rather than as comparative estimates.

Why does follow-up time matter?

In general, adverse-event counts are influenced by how long people are observed and how completely events are captured. A count accumulated over longer exposure may differ from a count over shorter exposure even when the underlying event rate is similar. Time-to-event or incidence-rate approaches can address follow-up time in different ways, but they require suitable timing information and an analysis plan. The registry gives the primary endpoint timeframe as an average of 2.72 years and lists Exposure Duration as a secondary outcome. It does not provide the individual follow-up distribution or a rate-based primary result in the information reported.

An average timeframe should not be interpreted as identical observation for every participant. It also does not tell readers whether follow-up ended for different reasons, whether all events were captured until the same endpoint, or how loss to follow-up was handled. Those details are not reported in the registry record. Without them, a reader cannot reconstruct person-time or determine how varying exposure affected the observed counts.

What can percentages for event terms tell the reader?

The record lists six serious adverse-event terms with percentages. These percentages identify the registry’s reported values for those terms, but the entry does not explain the denominator or whether terms can overlap within a patient. In general, event categories may overlap: one patient can experience more than one kind of event, and one event may be classified under a particular term according to coding rules. Without a stated denominator and coding explanation, the percentages should be reported as listed rather than converted into patient counts, summed, or interpreted as a distribution across exclusive categories.

The record does not provide definitions for the listed terms, severity grading, adjudication procedures, or an account of how the selection of the listed terms was made. General statistical interpretation: transparent definitions and ascertainment procedures help readers judge whether events were measured consistently and whether the reported categories are comparable across studies. Their absence in the registry entry limits that assessment.

What do planning calculations mean?

General explanation: sample-size planning asks how much information a future study might need to detect a specified effect under stated assumptions. The planning assumptions attached to this record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. Those are assumptions for planning illustrations, not a description of this extension’s single-group design. They do not show that the study was planned with those assumptions, and they do not measure the probability that the completed study detected an effect.

In particular, a planning illustration based on an observed effect is not observed power. Observed power is not a substitute for an estimate and its uncertainty, and a calculation based on a study result can be misleading as a measure of evidence. The registry does not report a sample-size justification for the extension. Any sample-size scenarios should therefore be understood as hypothetical planning aids rather than evidence about the study’s original design or its achieved precision.

What role do confidence intervals and over-dispersion have in general?

General explanation: a confidence interval communicates the range of estimates compatible with the data and a specified statistical procedure. It helps show precision, which a point estimate alone cannot convey. The registry entry does not report a confidence interval for the primary endpoint or the listed adverse-event counts. No interval can be inferred from the information reported without performing a new calculation, and no such recalculation is appropriate as a replacement for the sponsor’s analysis.

Over-dispersion is a general issue in count data when variability exceeds what a chosen model expects. If present, an analysis that assumes too little variability can understate uncertainty. Whether over-dispersion is relevant depends on the outcome and model. The registry record lists zero analyses and does not describe a count model or an over-dispersion assessment, so no conclusion about its presence or handling can be made for this study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment")
n      <- c(41)
events <- c(41)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment  41  41  100.0  91.4  100.0  91.4  100.0  91.6  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies treatment-emergent adverse events as the primary endpoint, with Exposure Duration as a secondary outcome. It lists zero analyses. A detailed statistical analysis plan, including any prespecified testing hierarchy, multiplicity adjustment, or interim-analysis procedure, is not reported in the registry record. Therefore, the record does not show whether multiple outcomes or repeated analyses were formally controlled for, or whether all planned analyses are represented.

Multiplicity is a general concern when many hypotheses are tested: the chance of at least one apparently notable result can increase as testing expands. The appropriate response depends on the study’s goals and prespecified analysis plan. Since no inferential analyses are listed, and no analysis plan is reported, it is not possible to determine what multiplicity procedures were intended or used. The absence of a listed procedure should not be interpreted as evidence that a specific procedure was or was not applied outside the record.

The registry does not report how missing outcome data were handled, whether any participants discontinued follow-up, or whether all enrolled participants contributed to each safety measure. It also does not explain whether the endpoint population differed from the enrolled population beyond the definition that patients received at least one dose of EFI. These details matter because incomplete or unequal observation can affect event counts and their interpretation.

General explanation: an analysis population defines which participants contribute to a particular estimate. Different choices can be appropriate for different questions, but they should be prespecified and described so readers can understand who is represented. The record names a primary-outcome population but does not give a complete account of exclusions, missingness, or analysis procedures. The resulting uncertainty should be acknowledged rather than filled in by assumption.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: catheter site infection (17.1%), pulmonary arterial hypertension (17.1%), lung transplant (14.6%), right ventricular failure (14.6%), device dislocation (9.8%).

The serious adverse-event entry reports 35 affected patients among 41 at risk in the treatment group. The entry for other adverse events reports 39 affected among 41 at risk. These are separate registry categories and should be read as recorded patient counts, not as event totals or rates. They are not evidence of a comparison against another treatment group, because the extension has no concurrent comparator.

The serious-event terms listed include Catheter site infection, 17.1%; Pulmonary arterial hypertension, 17.1%; Lung transplant, 14.6%; Right ventricular failure, 14.6%; Device dislocation, 9.8%; and Device related sepsis, 9.8%. These are the percentages as recorded. The registry entry does not state whether an individual could appear under more than one term, define the denominator for each percentage, or explain whether the listed terms represent all serious adverse events. They should not be summed or treated as mutually exclusive shares.

“Serious” is a registry category, not a statement that an event was caused by treatment. The record does not provide the adjudication, attribution, or coding details needed to make that determination. These figures describe reports in the extension and should be interpreted with the study’s open-label, single-group design and the absence of reported uncertainty estimates in mind.

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

The posted record establishes that the study was a completed, open-label extension in pulmonary arterial hypertension and that its stated purpose concerned safety and tolerability while allowing continued treatment after Study AC-066A301. It documents one treatment group, enrollment of 41, a primary endpoint of treatment-emergent adverse events, and an average timeframe of 2.72 years. The safety entries also give counts of affected patients and a list of serious-event terms with percentages.

Those observations are useful as descriptive registry information about the participants and events recorded in this extension. They do not supply a numerical result for the stated primary endpoint. Nor do the separate serious and other adverse-event entries necessarily constitute that primary endpoint: the record does not explicitly identify them as its result or explain how their definitions relate to it.

The record does not establish that Epoprostenol or ACT-385781A caused any particular adverse event. With no randomized comparator, differences from an alternative treatment or from no treatment cannot be estimated. The information also does not establish comparative effectiveness, because the described primary question is safety and tolerability and no efficacy comparison is reported. The listed serious-event terms should not be interpreted as exhaustive, exclusive categories or as causal findings.

The record’s limitations in reporting also constrain precision. It does not provide confidence intervals for the primary endpoint or adverse-event counts, detailed missing-data handling, individual follow-up durations, or a statistical analysis plan. The timeframe is stated as an average, so it does not imply equal follow-up for every participant. These gaps prevent a full assessment of uncertainty, event capture, and the analysis population.

The appropriately narrow conclusion is that the registry documents adverse-event reports among participants in a single-group extension, while leaving the primary endpoint’s numerical result and key analysis details unreported. That description neither proves the presence nor absence of a treatment effect on safety, and it cannot support a comparison the study was not designed to make.

14. Why This Trial Matters Statistically

This study illustrates why design determines what an outcome can mean. A safety endpoint can be important in an extension intended to support continued treatment, but the presence of an endpoint does not by itself make a result comparative. In this case, the open-label, nonrandomized, single-group design means that reported counts describe the treatment group’s experience. They do not estimate how those outcomes differ from a control group.

It also illustrates the distinction between outcome specification and outcome reporting. The registry names treatment-emergent adverse events as the primary endpoint, specifies the unit as number of patients, and gives an average timeframe of 2.72 years. Yet it does not report the numerical result for that endpoint. Separate adverse-event summaries add information, but cannot automatically be substituted for the missing primary result. Statistical interpretation depends on matching a result to its stated definition and population.

For biostatisticians and clinical researchers, this record also underscores the value of reporting uncertainty and follow-up details. Counts and percentages can be informative, but readers need to know their definitions, denominators, completeness, and precision. Here, the registry does not give confidence intervals, detailed event coding or attribution procedures, or a complete description of missing data and follow-up. That limits both reproducibility and the scope of interpretation.

Finally, planning calculations must remain distinct from the design actually conducted. The registry’s planning assumptions describe illustrative calculations for a two-arm comparison, whereas the extension is single-group. Such illustrations may aid future planning under stated assumptions, but they cannot be treated as original design justification, evidence of achieved power, or a remedy for the lack of a comparator. Keeping these distinctions clear prevents descriptive safety observations from being overstated.

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 extension’s most important design limitation for interpretation is the absence of a control group. Since allocation is not applicable and the study is nonrandomized and single-group, the record cannot establish a comparative event rate or separate treatment effects from the underlying condition, other care, or background events. Open-label conduct also means masking was absent, although the registry does not describe how that affected event reporting or assessment.

The record states an average timeframe of 2.72 years but does not report individual follow-up or exposure distributions. Exposure Duration is listed as a secondary outcome, but no result is included in the record details. Consequently, readers cannot assess how much observation varied across participants or interpret counts in relation to person-time. The registry also does not report how incomplete follow-up or missing safety information was handled.

The primary endpoint’s numerical result is not reported in the registry record. The available serious and other adverse-event entries provide counts, but the record does not explain whether these entries correspond to the primary endpoint, how events were defined, or how attribution and coding were determined. The listed serious-event percentages also lack an explained denominator and overlap rule.

Further limitations include the absence of reported confidence intervals and a detailed statistical analysis plan. The registry lists zero analyses, so it does not present inferential estimates for the outcomes described. Sample-size planning assumptions attached to illustrations do not document the extension’s original justification and cannot supply an uncertainty assessment for the observed results. These reporting gaps limit reproducibility and make it difficult to assess the precision and completeness of the safety findings.

Finally, the study is an extension of AC-066A301, and the registry describes its intended role as continuing treatment after participation in that study ended. The record does not provide enough detail to characterize how selection into the extension may affect generalizability. Its findings should therefore be understood in the context of this extension population rather than presumed to represent every patient with pulmonary arterial hypertension.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Epoprostenol for Injection in Patients With Pulmonary Arterial Hypertension — NCT01470144.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2016-12-09.
• 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

NCT01470144 is a completed Phase 3, open-label, nonrandomized, single-group extension study in pulmonary arterial hypertension. The official title describes an extension of Study AC-066A301 investigating the safety and tolerability of ACT-385781A. The listed intervention is Epoprostenol. The registry reports enrollment of 41, a start date of 2011-06-01, primary completion on 2015-06-01, and a primary-outcome timeframe described as an average of 2.72 years.

The primary endpoint is treatment-emergent adverse events, measured as the number of patients among those who received at least one dose of EFI. Its numerical result is not reported in the registry record. Separate safety entries report serious adverse events in 35 of 41 patients at risk and other adverse events in 39 of 41 patients at risk, with serious-event terms and percentages listed. No concurrent control group, confidence intervals, detailed analysis plan, or missing-data procedures are reported in the registry record. These observations are descriptive and do not establish causation or comparative safety.