A Extension Study of Udenafil in Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Extension Study of Udenafil in Adolescents (NCT03013751), a na phase 3 study. The primary outcome is Treatment-Emergent Adverse Events.

2. Clinical Question

The registry describes a Phase III extension study intended to supplement the FUEL Phase III clinical trial with safety information about longer-term udenafil use in adolescents with single ventricle congenital heart disease. Its primary endpoint counts participants with treatment-emergent adverse events in the Safety Population. The record also lists changes in maximal VO2, lnRHI, serum BNP, MPI, and child- and parent-reported PedsQL measures as secondary outcomes.

This is a safety-focused question, not a randomized comparison of udenafil with another treatment or with no treatment. The registry record therefore supports a description of events recorded among participants in the udenafil group, but it does not directly estimate how those events compare with what would have occurred under a different treatment or without udenafil. The record does not report a comparative efficacy question as the primary objective.

3. Trial Design

This is a Phase III extension study with a single-group model. The registry lists allocation as not applicable and masking as none. It describes one drug group: udenafil administered for 52 weeks. Enrollment is listed as 301, and the study status is completed. The record gives a start date of 2017-02-06 and a primary completion date of 2019-12-30.

The stated purpose was to supplement the FUEL Phase III clinical trial by providing safety information regarding long-term udenafil use in adolescents with single ventricle congenital heart disease. The extension framing is relevant to interpretation: the results describe experience during the study’s treatment period, rather than a randomized contrast between study groups. The record does not specify how participants entered the extension or how their participation related to individual records in the earlier trial.

The primary endpoint is treatment-emergent adverse events, counted as participants, over 52 weeks in the Safety Population. Listed secondary outcomes include changes in maximal VO2, log-transformed reactive hyperemia index (lnRHI), serum BNP, myocardial performance index (MPI), and PedsQL physical functioning and psychosocial health summary scores, with child- and parent-reported measures listed separately.

The registry record does not report the study’s eligibility criteria in the information, the distribution of baseline characteristics, or a statistical analysis plan. It also does not report why the enrollment target was selected. Those omissions limit assessment of how closely the enrolled group represents a broader adolescent population and how the study intended to handle the outcomes analytically.

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

Analysis population for the primary outcome, as defined in the registry: Safety Population

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 52 Weeks.

The primary endpoint is treatment-emergent adverse events, expressed as the count of participants in the Safety Population who experienced an event during the 52-week timeframe. This kind of endpoint is used in safety monitoring because it records whether participants experienced adverse events while under observation. It can provide a descriptive account of safety findings during an extension period.

The registry reports 54 participants with serious adverse events and 257 participants with other adverse events, with 301 listed at risk for each category. These are participant counts, not counts of event episodes. A participant may experience more than one event, and the registry figures do not establish whether the serious-event and other-event groups overlap. The registry also records 0 deaths.

The endpoint’s usefulness depends on how events were defined, collected, coded, and attributed. Those details are not reported in the registry record. The record also does not provide a comparison group, so the counts describe what was recorded during treatment but cannot by themselves separate treatment-related events from events associated with the underlying condition, background care, or other causes. They should be read as safety observations from this study, not as a comparative estimate of risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is defined as a count of participants with treatment-emergent adverse events, rather than a count of every event episode. In general, participant counts answer how many people experienced at least one event in the specified category. They do not reveal how often each person experienced an event, how long events lasted, or whether several events occurred in the same person. Those details require event-level reporting, which is not reported in the registry record.

The registry reports separate counts for serious adverse events and other adverse events. The categories should be interpreted as the record presents them. It does not explain whether participants can appear in both categories, so the counts should not be combined or treated as mutually exclusive groups. The record does not provide a definition of seriousness or the operational definition used for a treatment-emergent event.

Why is this not a treatment comparison?

In general, a randomized comparison uses differences between assigned groups to estimate how outcomes vary with treatment assignment. This study is listed as single-group, with allocation not applicable and no masking. There is no concurrent control group in the registry design. Its safety counts therefore describe the treated group; they do not estimate a between-group treatment effect.

Without a comparator, it is not possible to distinguish an event associated with treatment from an event that might have occurred because of the underlying condition, background care, or other factors. This is a limitation of the design for causal comparison, not a claim that the study’s descriptive safety observations are uninformative. Such observations can document what was recorded during the extension, while leaving comparative questions unanswered.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the data under a statistical model and conveys the precision of an estimate. The registry record does not report confidence intervals for the adverse-event counts. A confidence interval for a single-group event proportion, even if reported, would describe uncertainty around that group’s event frequency; it would not create a comparison with an untreated or alternative-treatment group.

In general, a hypothesis test evaluates data relative to a specified statistical question and assumptions. The registry lists 0 analyses and does not report a p-value or test for the primary endpoint. There is therefore no reported inferential result from which to assess statistical evidence for a treatment difference. In a single-group safety extension, the central posted information is descriptive rather than a randomized contrast.

What do the planning illustrations mean?

Any sample-size planning illustration based on an observed effect is a hypothetical design calculation, not observed power. In general, a planning calculation asks how many participants per arm might be needed under stated assumptions to detect a chosen effect. The assumptions described for these illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions do not describe this study’s single-group design, and the illustrations do not show that the study had a particular probability of detecting an effect. The registry record does not report that these assumptions were used to design the trial.

The record also does not report a sample-size justification for the extension. A planning illustration should therefore be read as a separate hypothetical exercise, not as evidence about why enrollment was set at 301 or whether the study was adequately powered for a safety or secondary-outcome question.

What do the secondary outcomes add?

The registry lists 11 outcome measures and 0 analyses. Secondary measures include maximal VO2, lnRHI, serum BNP, MPI, and child- and parent-reported PedsQL domains. These measures represent different types of physiological, laboratory, and reported outcomes. Their inclusion in the registry does not by itself establish that results were analyzed or that any particular change occurred. Results and statistical methods for these outcomes are not reported in the registry record.

When a study considers multiple outcomes, multiplicity can arise because many statistical questions are examined. In general, testing many hypotheses without an appropriate plan can increase the chance of obtaining apparently notable findings by chance. Whether adjustment or another multiplicity strategy was planned or used is not reported in the registry record. No conclusion about multiplicity control can be drawn from the outcome list alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary treatment-emergent adverse-event measure and secondary physiological, laboratory, and patient- or parent-reported outcomes. It records 0 analyses. Statistical results for the listed outcomes, including estimates of change and inferential summaries, are not reported in the registry record. The presence of an outcome in the listing should not be taken as evidence that its result was analyzed or posted.

When multiple outcomes are assessed, the chance of a false-positive finding can increase if many hypotheses are tested without a prespecified strategy. In general, studies may address this through a hierarchy of outcomes, adjustment procedures, or other approaches. Whether such a strategy was planned or applied is not reported in the registry record. No adjustment should be assumed.

Missing-data methods are not reported in the registry record. The available summary does not state how missing observations, withdrawals, or incomplete outcome assessments were handled. It also does not report the amount or pattern of missing data. Therefore, the posted record does not support an assessment of whether missingness could affect the outcome summaries.

The primary endpoint identifies the Safety Population, but other analysis populations and the rules used to define them are not reported in the registry record. The record does not state how participants were included in analyses of the secondary outcomes. These reporting gaps limit the ability to reproduce or evaluate the analyses and should not be filled by assumptions about the study protocol.

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 (1.3%), protein-losing gastroenteropathy (1.0%), transient ischaemic attack (1.0%), depression (1.0%), anaemia (0.7%).

The serious adverse-event summary lists 54 participants with serious events among 301 at risk. The separate other-adverse-event summary lists 257 participants among 301 at risk. The registry records 0 deaths. These are counts of participants, not counts of event episodes. The record does not say whether participants with serious events are also included in the other-event count, so the categories cannot be treated as mutually exclusive.

The listed serious-event terms and percentages are cardiac failure (1.3%), protein-losing gastroenteropathy (1.0%), transient ischaemic attack (1.0%), depression (1.0%), anaemia (0.7%), and supraventricular tachycardia (0.7%). These figures describe entries in the registry; they do not show that udenafil caused the events. The registry does not provide term-specific participant counts in the information, event timing, or details of how terms were coded and selected for display.

Because the study has no comparator, the counts cannot show how the event experience compares with another treatment or with no study treatment. They are descriptive observations from a 52-week safety extension, and interpretation is limited to the definitions and details recorded in the registry.

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

The registry record documents adverse-event experience during a 52-week udenafil extension study in adolescents with single ventricle congenital heart disease after Fontan palliation. It records 54 participants with serious adverse events, 257 with other adverse events, and 0 deaths. It also lists several serious-event terms with their associated percentages. These findings describe what the record reports for this study population and observation period.

The counts do not establish that udenafil caused any event, nor do they show how event frequency would compare with another treatment or no study treatment. The single-group design has no concurrent control, and the study was not masked. Thus the registry cannot answer a comparative safety question through these counts alone. The record also does not provide confidence intervals, statistical tests, or detailed event-level results that would quantify uncertainty or describe event course.

The endpoint is safety-focused. The listed secondary outcomes do not include posted analysis results in the registry information. It is therefore not possible to draw conclusions from this record about changes in those measures. The record also does not supply enough detail to evaluate missing-data handling, multiplicity procedures, or the statistical analysis plan.

These limits do not erase the descriptive value of the observations. The counts can inform readers about the events recorded among participants during the extension, while the design and reporting gaps define what the record cannot establish. The results should not be generalized automatically to other populations, observation periods, or treatment settings.

13. Why This Trial Matters Statistically

Extension studies address questions that differ from those answered by a controlled efficacy trial. They can describe adverse events observed while participants continue treatment over an extended period. This study’s stated purpose was to supplement the FUEL Phase III clinical trial with safety information about long-term udenafil use in adolescents with single ventricle congenital heart disease. Its 52-week timeframe and Safety Population endpoint fit that descriptive focus.

The design also illustrates why the form of a result matters. Participant counts can communicate how many people were recorded with an event, but they do not provide an event-by-event account or a comparative treatment effect. Without a concurrent control group, the recorded counts cannot separate treatment-associated events from those related to the underlying condition or other influences. The absence of reported inferential analyses further limits estimates of precision and statistical evidence.

For biostatistical interpretation, the record distinguishes a registry-listed outcome from a reported analysis result. It lists multiple secondary measures, but their results and analysis methods are not reported in the registry record. Similarly, a planning illustration based on an observed effect is a design exercise, not observed power and not evidence that the extension was sized according to that calculation.

The study is therefore statistically informative as a record of a single-group safety experience, while remaining limited for causal or comparative conclusions. Clear separation of descriptive counts, hypothetical planning calculations, and comparative evidence helps prevent overinterpretation of safety findings.

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 single-group design is the central limitation for interpreting treatment effects. There is no concurrent comparator, allocation is listed as not applicable, and masking is listed as none. The adverse-event counts therefore cannot quantify how safety outcomes differ from those under another treatment or without study treatment. They also cannot establish that a recorded event was caused by udenafil.

The registry record does not report detailed event definitions, collection procedures, coding rules, event timing, duration, recurrence, or clinical course. It does not clarify whether participants can contribute to both the serious-event and other-event categories. The serious-event terms are reported with percentages but without term-specific participant counts in the information.

Although the record identifies the Safety Population for the primary endpoint, it does not describe population definitions for other analyses. Missing-data methods, withdrawals, and the amount or pattern of missing observations are not reported. Statistical methods and results for the listed secondary outcomes are also not reported. This prevents evaluation of analytic choices, precision, and robustness.

The registry describes a 52-week extension, but does not report event experience beyond that timeframe. It also does not provide baseline characteristics or detailed eligibility criteria in the information, which limits assessment of the population’s representativeness. The registry record does not report a sample-size justification or whether the study was designed for a particular comparative or inferential safety objective.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Extension Study of Udenafil in Adolescents — NCT03013751.
• Registry record last updated 2025-12-09; status last verified 2025-11.
• Results first posted 2025-12-09.
• 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.

18. Record Summary

The registry record describes a completed Phase III, single-group extension study of udenafil in adolescents with single ventricle physiology after Fontan palliation. The study was intended to supplement the FUEL Phase III clinical trial with safety information. The intervention was udenafil administered for 52 weeks; the primary endpoint was treatment-emergent adverse events in the Safety Population.

The record lists 301 at risk for each adverse-event category, 54 participants with serious adverse events, 257 with other adverse events, and 0 deaths. It lists 11 outcome measures and 0 analyses. Secondary outcomes include physiological, laboratory, and PedsQL measures, but their analysis results are not reported in the registry record. Because there is no comparator, the adverse-event counts are descriptive and do not establish comparative safety or causation.