Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN) (NCT01069861), a na phase 2 study. The primary outcome is Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO).

2. Clinical Question

The clinical question was whether sildenafil could be used in newborns with PPHN and whether participants would go on to require standard therapy with iNO or ECMO. The registry's brief summary states the rationale that sildenafil is efficacious in newborns with PPHN and that its use will reduce the need for iNO. That statement describes the study's rationale; it is not an analyzed finding from this record.

The study enrolled 4 participants and was terminated. It did not use random allocation or a parallel control group. As a result, the central question is descriptive: how often did the listed participants require iNO or ECMO during the stated follow-up period? A single-group study cannot make a randomized, like-for-like comparison between sildenafil and another treatment or usual care. It also cannot separate the observed course from other factors that may influence clinical decisions or outcomes.

The outcome description specifies treatment required after failure of study treatment. The record says data for this outcome were collected and reported in individual participant listings, but were not statistically summarized for analysis because of early study termination. Consequently, the registry record does not report a summarized percentage that can answer the primary question. The listed secondary outcomes cover oxygenation measures, respiratory support, time to standard therapy, and sildenafil pharmacokinetics; their inclusion does not by itself establish that analyzable results were reported.

3. Trial Design

This was a Phase 2, single-arm, single-centre study of sildenafil in near-term and term newborns with PPHN. The registry records a single-group model, no masking, and allocation as not applicable. Enrollment was 4. The study status is terminated, and the primary outcome description attributes the lack of statistical summary to early termination.

The registry lists the study start as 2010-12 and primary completion as 2011-11. Its official title identifies the population as near-term and term newborns with PPHN. The listed intervention is sildenafil, although the intervention name is misspelled as “sildanefil” in the intervention entry. No separate comparator or control arm is described. The empty arm description does not add details about dosing, treatment procedures, or how participants were managed.

The primary outcome was the percentage of participants requiring iNO or ECMO after failure of study treatment, from the start of infusion through Day 14. Secondary outcomes included change from baseline in Oxygenation Index, differential saturation, and the arterial oxygen pressure to inspired oxygen fraction ratio at Hour 6 and Hour 12; duration of mechanical ventilation; time to receipt of iNO or ECMO; population pharmacokinetics of sildenafil; and maximum observed plasma concentration of sildenafil metabolite UK-103320. The registry lists 11 outcome measures overall.

The record does not describe a randomized allocation process, masking, a control treatment, or a comparative estimand. It reports 0 analyses. Thus, design features that would support a controlled treatment-effect estimate are not present in the registry record. Details such as the planned analysis population, sample-size justification, interim analyses, and a full statistical analysis plan are not reported in the registry record. The single-group structure permits description of observed events and measurements, but it does not provide a direct counterfactual comparison.

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: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to early study termination.

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 Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO), measured over From start of infusion (baseline) up to Day 14.

The primary endpoint was the percentage of participants requiring inhaled nitric oxide (iNO) or extracorporeal membrane oxygenation (ECMO) after failure of study treatment. The stated observation period ran from the start of infusion, defined as baseline, through Day 14. The endpoint combines two forms of standard therapy into a single outcome: whether a participant required either iNO or ECMO during that period.

This kind of endpoint can be used to describe whether participants subsequently needed additional or alternative respiratory support after the study treatment was considered to have failed. It is clinically interpretable as a treatment-escalation outcome, but it does not by itself measure the size of any treatment effect. In a single-arm study, an observed proportion would describe the enrolled group; without a concurrent comparison group, it cannot establish how that proportion differs from what would have occurred under another treatment or usual care.

The registry states that the outcome data were collected and reported in individual participant listings but not statistically summarized for analysis because the study ended early. Therefore, the registry record does not report a summarized percentage, an estimate of uncertainty, or an inferential comparison for this primary endpoint. The outcome's definition and timeframe are reported, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with no masking and allocation recorded as not applicable. These features determine what statistical questions the design can answer. With no randomized comparison group, the analysis can describe outcomes observed in the enrolled participants, but it cannot estimate a randomized difference between sildenafil and a control treatment. A descriptive percentage, if reported, would refer to this study group and its specified follow-up, rather than a comparative treatment effect.

What would a percentage endpoint represent?

For the primary outcome, the event is requiring iNO or ECMO after failure of study treatment during the stated period from the start of infusion through Day 14. A percentage would express the frequency of that event in the defined analysis population. To interpret it fully, a reader would need the event count, the relevant denominator, and clarity about how participants with incomplete follow-up or missing outcome information were handled. The registry says the data were collected in individual participant listings, but not statistically summarized. It does not report a summarized percentage or an analysis population for this endpoint.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the statistical method used. It communicates precision as well as the central estimate: a wider interval indicates greater uncertainty, while a narrower interval indicates more precision under the model's assumptions. A confidence interval does not correct for bias, create a control group, or prove that an intervention caused an outcome. No confidence interval for the primary endpoint is reported in the registry record.

With a small group, estimates are particularly sensitive to the outcomes of individual participants. General statistical methods for proportions can represent uncertainty, but the choice of method matters, especially when counts are sparse. The record does not specify a method for estimating uncertainty for the primary endpoint. It would therefore be inappropriate to infer an interval or a test from the endpoint definition alone.

Why does the single-arm design matter?

A treatment-effect estimate normally compares outcomes under different treatment strategies. Random allocation is one way to make those groups more comparable, in expectation, with respect to factors that could influence outcomes. This study has no randomized comparison: it is single group, and allocation is not applicable. An observed outcome may be influenced by the underlying condition, concurrent care, clinical decisions about escalation, and other factors. Without a comparator, the registry record cannot distinguish those influences from any effect of sildenafil.

The endpoint itself includes a decision to provide iNO or ECMO. Such an outcome can be clinically relevant, but it may also depend on clinical thresholds and local practice. The record identifies the event definition and follow-up period; it does not provide additional detail about decision criteria or standardization of those decisions. Such details are not reported in the registry record.

How should the planning calculations be read?

The sample-size assumptions describe a planning illustration computed from an observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. In general, sample-size planning asks how much information a hypothetical future study would need to detect a chosen effect under stated assumptions. It is a forward-looking design exercise, not a result of the completed study.

These planning illustrations should not be read as observed power. Observed power is not a substitute for examining an effect estimate and its uncertainty; a planning calculation likewise does not demonstrate that the intervention had an effect. The record does not report the trial's own sample-size justification or state that these hypothetical assumptions governed its design. The illustrations' assumptions also describe a two-arm allocation, whereas the trial itself is single group. That difference is important: the planning setup and the actual study design answer different questions.

The assumptions state that time-to-event planning tables use a total number of events, while other planning tables use participants per arm. Those are planning conventions, not observed counts from this study. The registry does list time to receipt of standard therapy as a secondary outcome, but the available record does not provide an analysis of that outcome.

What can be inferred from the outcome list?

The secondary outcomes include changes from baseline in oxygenation measures at Hour 6 and Hour 12, duration of mechanical ventilation, time to iNO or ECMO, and pharmacokinetic measures. These labels identify intended measurements, not analysis methods or numerical findings. A change-from-baseline outcome generally compares a follow-up measurement with a baseline measurement within a participant. Interpretation depends on how measurements were collected, how missing measurements were handled, and whether a group summary or model was used. Those analytic details are not reported in the registry record.

The registry reports 11 outcome measures and 0 analyses. The count of outcomes does not establish how many had complete data, how many were analyzed, or whether any statistical test was performed. The primary outcome description specifically says the data were not statistically summarized for analysis. For other outcomes, analysis details and results are not reported in the registry record. Readers should therefore distinguish between outcome definitions and statistical evidence: a defined endpoint tells what was intended to be measured, while an analysis would need to show how the collected data were summarized and with what uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary endpoint and multiple secondary outcomes. When a study examines many outcomes, there is a general risk that some findings may appear unusual by chance, particularly if many separate statistical tests are conducted. Statistical plans can address multiplicity by identifying a primary endpoint, specifying a testing sequence, or adjusting interpretation across multiple tests. The registry record does not report a multiplicity strategy or a statistical analysis plan, so it is not possible to determine how multiple outcomes were intended to be handled.

The record reports 0 analyses. For the primary outcome, it specifically states that data were collected and reported in individual participant listings but were not statistically summarized because of early termination. It does not provide a summarized estimate, an uncertainty interval, or a test for that endpoint. The secondary outcome names and time points do not establish that complete measurements or analyses are available.

Missing-data handling and analysis populations are not reported in the registry record. The record does not specify whether all enrolled participants were included in each outcome analysis, how incomplete follow-up was treated, or whether any particular population definition was used. Without these details, readers cannot assess whether the analysis denominator matched the enrolled group or whether missing information could have affected an estimate. The outcome listings are not a substitute for an explicit account of missingness and the analysis population.

The study was terminated, but the registry does not report an interim-analysis plan, a stopping rule, or the reason for termination beyond identifying early termination as the reason the primary outcome was not statistically summarized. These details are not reported in the registry record and should not be inferred.

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: congenital pneumonia (25.0%), persistent foetal circulation (25.0%).

The registry lists the Sildenafil group as having 4 participants at risk for serious adverse events, with 1 affected. For other adverse events, it lists 4 at risk and 3 affected. These are descriptive counts from a single group, not comparisons with another treatment. The record also lists congenital pneumonia and persistent foetal circulation among the top serious-event terms, each recorded as 25.0%.

These figures require cautious interpretation. A count of participants affected does not, by itself, establish that an event was caused by sildenafil. The record does not provide a comparator group that could show whether these events occurred more often than under another treatment or usual care. It also does not provide further event-level details in the registry record for this analysis, such as timing, severity grading beyond the serious-event classification, or an assessment of causality. Such details are not reported in the registry record.

The top serious-event percentages should be read as registry entries, not as estimates of comparative risk. The registry record does not report deaths. The small enrollment and lack of a control arm limit what can be concluded from the adverse-event counts; they cannot establish either a treatment-related safety effect or its absence.

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

The record establishes that a Phase 2, single-arm study of sildenafil in near-term and term newborns with PPHN enrolled 4 participants and was terminated. Its primary question was whether participants required iNO or ECMO after failure of study treatment during follow-up from the start of infusion through Day 14. The registry says information for this endpoint was collected in individual participant listings but not statistically summarized for analysis because of early termination.

That means the posted record does not provide a summarized primary-outcome percentage or a statistical estimate of its precision. It does not support a quantified conclusion about the frequency of standard-therapy use in the study group based on an analyzed result. The outcome definition indicates what the study intended to measure, but an endpoint definition is not itself evidence of an outcome.

The record also does not permit a causal comparison. With a single group and no randomized control arm, any observed clinical course could reflect the underlying condition, other aspects of care, or clinical decisions as well as the study intervention. No statistical method can recover a randomized comparison that the design did not include. The absence of a summarized result should not be interpreted as evidence for or against a treatment effect.

The adverse-event listings provide descriptive counts and terms, but do not establish treatment causality or comparative safety. The record lists serious adverse events affecting 1 of 4 at risk and other adverse events affecting 3 of 4 at risk; the listed serious-event terms are each 25.0%. These observations do not show how the same participants would have fared under another treatment. Deaths are not reported in the registry record.

In short, the registry documents the study question, design, enrollment, termination, outcomes, and limited safety information. It does not report a statistically summarized primary finding or a controlled estimate of efficacy or safety. Those boundaries are central to interpreting what this trial can and cannot establish.

13. Why This Trial Matters Statistically

This trial is statistically notable because a clearly defined primary outcome does not come with a statistically summarized result in the registry record. The endpoint concerns escalation to iNO or ECMO after failure of study treatment, a clinically interpretable event. Yet the registry says that data were collected only in individual participant listings and were not statistically summarized because of early termination. The distinction between collecting outcome data and producing an analyzable estimate is important: measurement alone does not provide a group-level result or its precision.

The study also illustrates the limits of a single-group design for questions about treatment effects. A single-arm study can describe the experience of its participants, but a controlled comparison is needed to distinguish an intervention-related difference from other influences on outcomes. The registry's allocation entry is not applicable, its model is single group, and it lists no comparator. The results therefore cannot support a like-for-like treatment contrast.

Small enrollment adds another statistical constraint. With 4 participants, the experience of each participant can have a strong influence on descriptive findings. Any resulting estimate would require careful attention to uncertainty and generalizability, and the registry does not provide a primary-outcome estimate or precision measure to assess. The safety counts should likewise be treated as descriptive, not as evidence of comparative risk.

Finally, the registry lists 11 outcome measures but reports 0 analyses. That contrast highlights why outcome registration and results reporting are different: a list of intended outcomes is not a substitute for methods, analyzed denominators, estimates, and uncertainty. The study's planning illustrations also need to be separated from trial findings. They are described as hypothetical calculations based on an observed effect, not as the study's own design or as observed power. Together, these features make the record a useful example of why design, analysis, and reporting must be considered alongside endpoint definitions.

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 most direct limitation is the absence of a statistically summarized primary outcome. The registry says primary-outcome data were collected in participant listings but not summarized because of early termination. As a result, the record does not provide the event percentage, an estimate of uncertainty, or a statistical comparison for the endpoint.

The design is single arm and single centre, with no randomized comparator. It can describe the enrolled participants' experience, but cannot provide a controlled estimate of the effect of sildenafil. The registry does not report a control treatment, an analysis population, or procedures for handling missing measurements. Details of treatment dose, outcome adjudication, or criteria for starting iNO or ECMO are also not reported in the registry record.

Enrollment was 4, limiting the amount of information available for describing outcomes and safety. The registry lists multiple outcomes, but does not report statistical analyses; it also does not report a multiplicity plan or a statistical analysis plan. Consequently, there is no basis in the record to determine how outcome selection, missing data, or multiple testing may have been addressed.

The study status is terminated, but the reason for termination beyond the stated early termination is not reported in the registry record. Nor are an interim-analysis plan, stopping rule, or sample-size justification reported. The planning assumptions described for hypothetical calculations should not be mistaken for the trial's own design assumptions. These limitations mean that the record supports description of the registered study and its reported safety counts, but not a firm estimate of treatment effect or a broad conclusion about safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN) — NCT01069861.
• Registry record last updated 2021-02-01; status last verified 2021-01.
• Results first posted 2012-12-03.
• 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

NCT01069861 is a Phase 2, single-arm, single-centre study of sildenafil in near-term and term newborns with PPHN. The registry lists no masking, allocation as not applicable, enrollment of 4, and terminated status. The study dates are recorded as start 2010-12 and primary completion 2011-11.

The primary outcome was the percentage requiring iNO or ECMO after failure of study treatment, from the start of infusion through Day 14. The registry says those data were collected in individual participant listings but were not statistically summarized because of early termination. It lists 11 outcome measures and 0 analyses. The record does not provide a summarized primary result or a controlled comparison.

For safety, the Sildenafil group lists 1 of 4 at risk as affected by serious adverse events and 3 of 4 at risk as affected by other adverse events. Congenital pneumonia and persistent foetal circulation are each listed at 25.0%. Deaths are not reported in the registry record.