To Provide Sildenafil Therapy To Eligible Adult Patients With Pulmonary Arterial Hypertension For 112 Weeks: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Provide Sildenafil Therapy To Eligible Adult Patients With Pulmonary Arterial Hypertension For 112 Weeks (NCT00946114), a registered phase not stated study. The primary outcome is Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The study title describes sildenafil therapy for 112 weeks. The primary safety outcome has a timeframe of baseline up to 116 weeks. These are both stated in the registry record; the reason for the difference is not reported in the registry record.

3. Trial Design

This was a local, multi-centre, open-label access study in Poland. Its stated purpose was to provide sildenafil to eligible adults with pulmonary arterial hypertension, including patients who had completed the A1481142 study, before reimbursement and availability for patients in Poland. The brief summary says that safety and tolerability data would be collected. The record is marked completed.

The study began in 2006-06, and primary completion is recorded as 2009-03. Enrollment is recorded as 32. The registry lists two sildenafil groups, titled Sildenafil 60 mg and Sildenafil 240 mg. It does not explain the process by which participants entered those groups or whether the listed doses reflect assigned treatment, changes in dose, or another arrangement. Allocation is not stated.

Open-label means that the study was not described as masked. The record does not report a randomized allocation, and explicitly cautions against treating the dose groups as a like-for-like control comparison. The posted counts therefore describe safety observations in each group; they should not be read as an estimate of the causal effect of one dose compared with the other.

The primary outcome covers adverse events from baseline up to 116 weeks. The safety-population description assumes that subjects took at least one dose. Non-serious adverse events were reported up to 7 days after the last dose, while serious adverse events were reported up to 28 days after the last dose. The reason that these follow-up windows differ from the 112-week duration in the study title is not reported in the registry record.

The registry record lists one outcome measure and zero analyses. It does not report a formal comparative analysis, a protocol, or a statistical analysis plan. This is consistent with reading the posted information as descriptive safety reporting rather than as a randomized efficacy trial.

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 population: all subjects assumed to have taken at least one dose of study medication. Non-serious adverse events were reported up to 7 days after the last dose of study medication. Serious adverse events were reported up to 28 days after the last dose of study medication.

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 Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline up to 116 Weeks.

The primary outcome is the number of subjects with adverse events and serious adverse events. Its unit is participants, and its parameter is recorded as a number. It therefore concerns how many participants experienced an event, not the total number of event episodes. A participant may experience more than one event, so participant counts should not be interpreted as event counts.

The record defines an adverse event broadly as an untoward medical occurrence after study medication, regardless of whether it was judged related to the medication. The examples include abnormal test findings, clinically significant signs or symptoms, changes in physical examination findings, hypersensitivity, worsening of underlying disease, and exposure in utero. A serious adverse event is defined by consequences such as death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, or a congenital anomaly or birth defect.

Safety and tolerability were the stated focus, so counting participants with adverse events is relevant to documenting what occurred while treatment was provided. These counts do not by themselves establish that treatment caused an event. The outcome also does not measure improvement in pulmonary arterial hypertension or another clinical benefit. An efficacy endpoint is not reported in the registry record.

The timeframe is baseline up to 116 weeks, with different reporting windows after the last dose for non-serious and serious events. The record does not report further details about event adjudication or how the counts were handled if a participant experienced multiple events of the same type.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods concern how data are summarized and how uncertainty is assessed. In this study, the available primary outcome is a count of participants with adverse events and serious adverse events. The registry record lists one outcome measure and zero analyses, so it does not report a formal statistical comparison between the dose groups.

What does a participant count represent?

A participant count records the number of people who experienced an event, rather than the total number of event episodes. This distinction matters because a person may experience several adverse events. Counting participants answers how many people were affected at least once within the outcome definition; counting events would answer a different question about the volume of recorded episodes. The posted primary outcome uses participants as its unit.

The group summaries identify counts at risk and counts with events. For serious adverse events, the record gives 8 participants among 20 at risk for Sildenafil 60 mg and 2 among 12 at risk for Sildenafil 240 mg. For other adverse events, it gives 11 among 20 and 8 among 12, respectively. These are descriptive summaries. No confidence interval, p-value, or adjusted estimate for a difference is reported in the registry record.

Why does allocation matter?

Random assignment, when used and properly implemented, can make treatment groups comparable on average with respect to factors known and unknown at baseline. That is why a randomized comparison can support a causal interpretation more strongly than a simple comparison of observed groups. This is general statistical context, not a claim about this study: the record does not state that participants were randomized, and it warns that the arms are not a like-for-like control comparison. The difference in observed counts therefore cannot isolate a dose effect.

Open-label describes a study in which treatment is not masked in the study description. In general, knowledge of treatment can affect reporting, assessment, or care decisions. The registry record does not describe how these possibilities were addressed, so their impact cannot be assessed from the posted information.

What does a confidence interval add?

In general, a confidence interval expresses statistical uncertainty around an estimate, such as an event proportion or a difference between groups. Its width depends on the amount of information and the variability in the data. An interval can help readers distinguish a relatively precise estimate from one that remains uncertain. The registry record does not report confidence intervals for these safety counts, so their statistical precision cannot be assessed using interval estimates from the posted results.

What can the planning illustration establish?

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 that the effect to detect is a stated fraction of the observed effect. Such calculations are hypothetical planning aids: they describe the sample size that a future design might require under specified assumptions. They are not observed power for the completed study and do not establish that the observed result is reliable or likely to replicate. Numerical planning results are not reported in the registry record.

The record also distinguishes the type of planning quantity by outcome: time-to-event planning tables use a total number of events, while other planning tables use participants per arm. That distinction is general to the stated planning description. The primary endpoint in this study is a participant count, not a time-to-event outcome. The registry record does not provide a time-to-event analysis for this endpoint.

Why do event definitions and follow-up windows matter?

Safety counts depend on the operational definition of an event and the period during which events are collected. Here, adverse events are defined broadly and irrespective of causality. Non-serious events were reported up to 7 days after the last dose, while serious events were reported up to 28 days after the last dose. In general, differing observation windows can affect how many events are captured, so comparisons between categories require attention to those windows. The record does not report a rationale for the different periods or a method to account for exposure time.

The study title specifies 112 weeks, while the primary outcome timeframe is baseline up to 116 weeks. These descriptions do not match exactly. The registry record does not report an explanation, so the exact relationship between the intended study duration and the primary safety assessment period remains unclear.

The serious-event terms are listed with percentages, but the denominator and selection method are not reported. General statistical practice would require knowing those details before treating percentages as estimates of risk or comparing them across terms. Since the details are absent, the listed terms are best read as reported descriptive entries, not as a complete or comparable ranking of event risks.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or statistical tests are assessed: the more opportunities to identify a result as noteworthy, the greater the chance of a misleading finding if no adjustment or prespecified hierarchy is used. This is general statistical context. The registry record lists one outcome measure and zero analyses, and does not report a statistical analysis plan, a hierarchy of endpoints, or any multiplicity adjustment. It is therefore not possible to determine whether additional analyses were planned or how multiple testing would have been handled.

The primary endpoint combines the reporting of adverse events and serious adverse events, and the record separately lists serious adverse event terms. It does not specify whether each term was prespecified, how overlapping terms were handled, or whether the displayed terms represent all events meeting the definition. The percentages attached to the listed terms have no stated denominator in the registry record.

Missing-data methods are not reported in the registry record. The safety population is described as all subjects assumed to have taken at least one dose, but the record does not state how missing follow-up, incomplete event reporting, withdrawal, or incomplete exposure information was handled. It also does not report participant-level follow-up or the number of participants with unavailable outcome data. Consequently, the completeness of the safety summaries cannot be evaluated from the registry information.

The registry record does not describe additional analysis populations beyond the safety population, nor does it report how the analysis population was defined for each dose group. It provides no imputation method or sensitivity analysis. These omissions mean that the reported counts should be interpreted as the posted descriptive safety summaries, without assuming that missing information was absent or resolved in a particular way.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sudden cardiac death (16.7%), cardiac failure (15.0%), cardiac arrest (5.0%), supraventricular tachycardia (5.0%), retinal vein thrombosis (5.0%).

The serious adverse event counts are 8 participants among 20 at risk in the Sildenafil 60 mg group and 2 participants among 12 at risk in the Sildenafil 240 mg group. The other-adverse-event counts are 11 among 20 at risk and 8 among 12 at risk, respectively. The endpoint counts participants with an event; they are not counts of every event episode and should not be added across event categories.

The serious adverse event definition is based on specified consequences, including death, life-threatening events, hospitalization or its prolongation, significant disability or incapacity, and congenital anomaly or birth defect. The record says serious events were reported up to 28 days after the last dose; non-serious events were reported up to 7 days after the last dose. The stated primary outcome timeframe is baseline up to 116 weeks.

The listed serious-event terms include Sudden cardiac death, 16.7%, and Cardiac failure, 15.0%, as well as four terms each listed at 5.0%. The registry record does not report the denominator or the method used to produce this list. The death fields for the groups are not populated; that is not evidence that there were no deaths. These descriptive entries do not establish that sildenafil caused the events or that one dose is safer than the other.

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

The registry record documents safety observations from an open-label access study intended to provide sildenafil therapy to eligible adults with pulmonary arterial hypertension in Poland. It reports participants with adverse events and serious adverse events in two dose groups, along with a list of serious adverse event terms. These observations are descriptive and relate to the stated safety follow-up windows.

The counts do not show that sildenafil caused or prevented any particular event. Adverse events were defined regardless of causality, and there is no reported randomized allocation or like-for-like control group. The comparison between the two dose groups cannot be treated as a causal estimate. The registry record does not report an adjusted analysis, uncertainty intervals, or a formal comparative test.

The record also does not answer an efficacy question. Its brief summary says that only safety and tolerability data would be collected, and the primary outcome is a count of participants with events. Improvement in pulmonary arterial hypertension or another benefit outcome is not reported in the registry record. The absence of an efficacy result should not be interpreted as evidence for or against a treatment effect.

The counts need to be read alongside their denominators and outcome definitions. They represent participants with events, not the total number of episodes. The serious adverse event list includes percentages, but the record does not state the denominator or how terms were selected. The missing death entries cannot be interpreted as zero deaths. The registry record also does not describe missing-data handling or provide participant-level follow-up, limiting assessment of completeness.

In short, the posted results describe reported safety events during an access study. They do not establish a causal dose comparison, quantify treatment benefit, or provide a complete account of statistical uncertainty. The study remains informative as a record of the safety outcomes collected under its stated definitions and reporting windows, subject to the design and reporting limitations.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between collecting safety information and testing a comparative hypothesis. The study was designed to provide access to sildenafil and collect safety and tolerability data. The primary outcome counts participants with adverse events and serious adverse events, rather than measuring efficacy. That purpose should guide how the numbers are interpreted.

The two dose groups are not described as randomized, and the registry record explicitly cautions that they are not a like-for-like control comparison. A numerical contrast between groups may look straightforward, but without a design that supports comparability it cannot be taken as evidence that dose explains the difference. This is a central principle of clinical-trial interpretation: the design determines which conclusions the data can support.

The endpoint also demonstrates why definitions and follow-up periods matter. The record uses a broad adverse-event definition and distinguishes reporting windows after the last dose for non-serious and serious events. Counts cannot be interpreted fully without understanding what qualifies as an event, when it could be captured, and how complete follow-up was. Some of those details are not reported in the registry record.

Finally, the record lists one outcome measure and zero analyses. Without reported inferential estimates or uncertainty intervals, readers have descriptive counts but no formal quantification of comparative uncertainty. Planning illustrations based on an observed effect, where available, would be hypothetical design calculations, not observed power. The study is therefore a useful example of how access-study safety data can be clinically informative as surveillance while remaining limited for causal comparisons or efficacy claims.

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 is the lack of a stated allocation method. The registry record says the arms are not a like-for-like control comparison, so the observed group counts cannot support a causal comparison of Sildenafil 60 mg and Sildenafil 240 mg. The record does not report baseline characteristics that would show whether the groups were comparable.

The study is described as open-label. The registry record does not state how event ascertainment was conducted, whether events were independently adjudicated, or whether assessors were masked. It also does not report whether the event terms were prespecified or how terms were selected for the serious-event list.

The record describes the safety population as subjects assumed to have taken at least one dose, but does not provide details about missing outcome data, withdrawals, completeness of follow-up, or exposure duration by participant. It does not report imputation or sensitivity analyses. The death entries are missing rather than stated as zero, and the percentages for serious-event terms have no reported denominator.

There is a difference between the 112-week duration in the study title and the baseline-up-to-116-weeks timeframe for the primary safety outcome. The reason is not reported in the registry record. The record also does not report an efficacy outcome, a statistical analysis plan, an inferential comparison, or uncertainty intervals. These limitations restrict interpretation to the posted descriptive safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Provide Sildenafil Therapy To Eligible Adult Patients With Pulmonary Arterial Hypertension For 112 Weeks — NCT00946114.
• Registry record last updated 2021-02-01; status last verified 2021-01.
• Results first posted 2010-03-30.
• 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

NCT00946114 is recorded as a completed, local, multi-centre, open-label access study in Poland. Its stated purpose was to provide sildenafil to eligible adults with pulmonary arterial hypertension, including patients who completed the A1481142 study, before reimbursement and availability for patients in Poland. The recorded enrollment is 32. The study began in 2006-06, with primary completion in 2009-03.

The primary outcome is the number of subjects with adverse events and serious adverse events, assessed from baseline up to 116 weeks. The record lists Sildenafil 60 mg and Sildenafil 240 mg groups and reports participant counts for serious and other adverse events. It lists one outcome measure and zero analyses.

The registry record does not state allocation and cautions that the groups are not a like-for-like control comparison. It describes the collected data as safety and tolerability information, not an efficacy assessment. The reason for the difference between the 112-week study title and the 116-week outcome timeframe is not reported in the registry record.