This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Chronic Sildenafil for Severe Diaphragmatic Hernia (NCT00133679), a randomized phase 4 study. The primary outcome is Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00133679 |
| Phase | Phase 4 |
| Condition | Hernia, Diaphragmatic, Hypertension, Pulmonary, Hypoplasia, Pulmonary |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
The intended population was infants with severe congenital diaphragmatic hernia. The registry summary describes severity as prolonged pulmonary hypertension or prolonged oxygen supplementation while receiving mechanical ventilation. The record does not report further eligibility details, participant characteristics, or how many infants in each arm contributed outcome data.
Intervention
The intervention was sildenafil for 45 days. The trial was listed as Phase 4. The registry record does not report the dose, route, dosing schedule, adherence, or treatment actually received by participants.
Comparator
The comparator was placebo for 45 days. The study was registered as randomized, quadruple-masked, and parallel-group. The record does not describe the placebo formulation or provide details about who was masked or how masking was maintained.
Primary question
The primary question was whether estimated systolic pulmonary arterial pressure at the final echocardiogram differed after treatment. The assessment timeframe was 7 weeks. The record says the study was terminated and that efforts to locate the data were exhausted because data had been lost or destroyed. Consequently, it gives no arm-level measurements or treatment contrast with which to answer the question.
3. Trial Design
The registry describes a randomized, quadruple-masked, parallel-group Phase 4 trial comparing sildenafil with placebo. The registered treatment durations were 45 days in each arm. Randomization is intended, in general, to reduce systematic differences between treatment groups at the start of a study. Masking is intended to limit the influence of treatment knowledge on care, measurement, and assessment. These design features describe how the trial was planned; without participant-level information or trial results, they do not establish that randomization or masking was successfully implemented.
The listed enrollment is 9. The record does not say how many participants were assigned to each arm, received treatment, completed follow-up, or had a final echocardiogram. The registry lists the study start as 2006-02 and primary completion as 2013-07, with status TERMINATED. It does not report why the trial was terminated, so the reason should not be inferred from the status alone.
The intended primary assessment was estimated systolic pulmonary arterial pressure at the final echocardiogram, with a timeframe of 7 weeks. The registry’s primary-outcome description says the study was terminated and that the data were lost or destroyed after efforts to locate them were exhausted. There are no primary-outcome values or reported analyses in the record. The record also lists secondary outcomes concerning vasoactive substances, adverse effects, growth, neurodevelopment, and respiratory status. Their presence in the registry does not mean that measurements or analyses are available.
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
| Stage | Sildenafil | Placebo |
|---|---|---|
| STARTED | 0 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
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.
Population: Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
| Characteristic | Unit | Sildenafil | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Age, Categorical: <=18 years | — | — | — | |
| Age, Categorical: Between 18 and 65 years | — | — | — | |
| Age, Categorical: >=65 years | — | — | — | |
| Sex: Female, Male: Female | — | — | — | |
| Sex: Female, Male: Male | — | — | — | |
| Region of Enrollment: United States | participants | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram, measured over 7 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was estimated systolic pulmonary arterial pressure at the final echocardiogram, assessed at 7 weeks. This is a measure of pressure in the pulmonary artery, estimated by echocardiography rather than reported as a direct invasive measurement. In general, pulmonary arterial pressure is relevant to a trial focused on pulmonary hypertension because it gives a physiological measure related to pressure in the lung circulation. The trial summary identifies estimated pulmonary artery systolic pressure as the measure used to assess the treatment question.
The registry does not specify the unit, the echocardiographic estimation method, the individual measurement protocol, or the statistical summary intended for the endpoint. It also gives no observed values, measure of variability, or comparison between sildenafil and placebo. Thus, the endpoint’s intended clinical and physiological role can be described, but its observed distribution and any treatment-associated difference cannot be evaluated.
An endpoint measurement is not, by itself, evidence about outcomes such as survival, development, or respiratory status. Those topics appear among the listed secondary outcomes, but their results are not reported in the registry record. No conclusion about the size, direction, or precision of an effect on pulmonary pressure can be drawn from the available primary-outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry does not contain the primary-outcome data. It states that the trial was terminated and that all efforts to locate the data were exhausted, with data lost or destroyed. As a result, there is no reported sildenafil value, placebo value, treatment contrast, or analysis for estimated systolic pulmonary arterial pressure at the final echocardiogram. The clinical question therefore remains unanswered by the posted results.
This is different from a result showing little or no difference. A null or small estimated contrast would require observed data and an analysis; neither is reported. The record also does not provide a confidence interval or other measure of uncertainty for the treatment contrast. A confidence interval, in general, describes the precision of an estimate and the range of effects compatible with the data under the analysis assumptions. Without an estimate and its uncertainty, it is not possible to distinguish a precise result near no difference from a highly uncertain result.
The listed enrollment is 9, but that value does not reveal how many participants were assigned to each arm or contributed the primary endpoint. No group-specific sample sizes for the outcome are reported. A small enrollment can make estimates less precise in general, but the record does not permit a calculation of precision or an assessment of whether the planned enrollment was achieved. Nor does enrollment alone show whether the trial was adequately powered.
The registry lists six outcome measures and zero analyses. The zero analyses indicate that no analysis entries are reported in the registry record; they should not be interpreted as evidence that a particular statistical test returned no effect. The primary outcome is marked as not reduced to one comparison because it has several categories or time points. Since no outcome data are available, there is no basis for choosing among possible comparisons or interpreting a particular time point or category.
The adverse-event record lists zero participants at risk, zero affected participants, and zero deaths in both the sildenafil and placebo groups. In the context of missing trial data and zero participants recorded at risk, those registry entries do not establish that no adverse events or deaths occurred. They indicate that the record contains no usable group-level safety counts. The listed secondary outcomes likewise cannot be treated as observed findings.
Any sample-size illustrations based on an observed effect are planning calculations, not observed power. They cannot replace missing outcome data or establish the result of this trial. No treatment recommendation or efficacy conclusion follows from a design description, a listed enrollment, or a missing result.
9. Statistical Methods Explained
Several statistical ideas help clarify what can and cannot be learned from the registry record. They are general explanations, not descriptions of analyses known to have been carried out in this trial. The record reports a randomized, quadruple-masked, parallel design, but does not report a statistical analysis plan or analysis results.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance process. Its purpose is to reduce systematic differences between groups, including differences in measured and unmeasured characteristics, so that a contrast in outcomes can be interpreted as an estimate of the treatment effect under the trial conditions. Randomization does not guarantee that groups will be identical, especially in a small study. It also cannot correct for unavailable outcomes, departures from assigned treatment, or a poorly defined analysis. The registry does not give the sequence-generation method, concealment procedures, group assignments, or a baseline comparison, so implementation cannot be assessed.
What does masking contribute?
Masking can reduce the chance that knowledge of assigned treatment influences participants’ behavior, clinical management, outcome measurement, or interpretation. The record labels masking as quadruple, but does not identify which roles were masked or describe the procedures. The designation alone is not evidence that masking remained intact. Because the primary endpoint involved an echocardiographic estimate, consistent measurement procedures would matter to interpretation in general; the registry does not report those procedures.
How would a treatment contrast be interpreted?
For a continuous endpoint such as estimated systolic pulmonary arterial pressure, a trial analysis might report a group-level summary for each arm and a contrast between arms. The choice of summary and model depends on the outcome distribution, measurement scale, design, and prespecified analysis plan. The registry gives no unit, endpoint values, dispersion measure, or model, so no particular contrast can be reconstructed. A difference in means, a model-adjusted contrast, or another summary must not be assumed to have been used.
Uncertainty is important alongside an estimated effect. In general, a confidence interval expresses how precisely the effect is estimated under the chosen statistical model. Its width is influenced by factors such as the amount of information in the data and variability in the outcome. A p-value, if reported, would address compatibility with a specified null model under assumptions; it would not measure clinical importance or the probability that a treatment works. No confidence interval, p-value, standard error, or variability estimate is reported for this endpoint.
Why can outcome distribution matter?
Statistical models make assumptions about how observations vary. For count outcomes, for example, a simple model may assume that the mean and variance are linked in a particular way. Over-dispersion means that observed variability is greater than the model allows; if ignored, standard errors can be too small and uncertainty can be understated. This is a general consideration and not a finding about this trial. The primary endpoint is a pressure estimate, and the record does not report its distribution or the model used. It would be inappropriate to assert that over-dispersion or another distributional problem occurred.
Likewise, repeated measurements or multiple outcome categories may call for methods that account for their structure. The registry notes several categories or time points for the primary outcome and does not reduce these to one comparison. It does not specify a repeated-measures model, a selected time point beyond the final echocardiogram, or a rule for combining categories. No such method can be attributed to the trial.
What do the planning assumptions mean?
The sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They define the effect to detect as a stated fraction of an observed effect. These are assumptions for planning calculations, not evidence about the trial’s original design or its results. The record does not report the protocol’s sample-size justification, and any calculated sample sizes are planning illustrations rather than observed power. An observed effect used as a planning reference does not establish that the effect is reliable or clinically important, particularly when primary-outcome data are stated to be unavailable in the registry record.
In general, power is a design property calculated under specified assumptions about an effect, variability, analysis, and sample size. It is not a measure of the probability that a result is true, and it cannot be recovered from the enrollment listing alone. The registry does not report a trial-specific power calculation or the assumptions used in any original design justification.
Finally, an analysis population must be defined to explain which participants contribute to an estimate. Common approaches may include analyzing participants according to randomized assignment or according to treatment received, but those approaches answer different questions and have different risks of bias. The registry does not report an analysis population, treatment adherence, exclusions, or missing-outcome handling. The lost data prevent these choices from being evaluated or an analysis from being reproduced.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures, including the primary endpoint and secondary outcomes related to vasoactive substances, adverse effects, growth, neurodevelopment, and respiratory status. When multiple outcomes, time points, or categories are examined, the chance of finding an apparently notable result by chance can increase. Statistical approaches can address multiplicity, for example by defining a primary comparison in advance or adjusting inference across comparisons. These are general methods; the record does not report a multiplicity strategy, outcome hierarchy beyond the designated primary outcome, or a statistical analysis plan.
The primary-outcome entry notes several categories or time points and is not reduced to one comparison. That leaves the exact intended analysis unclear. The record does identify the final echocardiogram and a 7 weeks timeframe, but does not report how other categories or time points were to be handled. It also reports zero analyses, so no multiplicity-adjusted or unadjusted result is available.
Missing-data handling is especially consequential because the primary-outcome description says the data were lost or destroyed. The registry does not report whether any individual endpoint measurements remain, the extent or pattern of missingness, or any imputation or sensitivity analysis. No missing-data method should be inferred. The record also does not define an analysis population or say whether analyses were to follow randomized assignment.
The adverse-event counts show zero participants at risk in each arm, so they do not provide a basis for safety comparisons. The lack of reported counts should not be interpreted as proof of no adverse events. The same caution applies to the secondary outcomes: their listing is not evidence that data were collected or analyzed.
11. What the Result Does, and Does Not, Mean
The registry record documents a trial question and design, but not an answer to the treatment question. It describes a randomized, quadruple-masked comparison of sildenafil and placebo in infants with severe congenital diaphragmatic hernia, with estimated systolic pulmonary arterial pressure at the final echocardiogram as the primary endpoint. The record also identifies a 7 weeks timeframe and 45-day treatment periods. Those details establish what the study was intended to examine, not what the comparison found.
Because the primary data are described as lost or destroyed, the posted record gives no estimate of the effect, direction of any difference, or precision. It does not show that sildenafil lowered pressure, raised pressure, or had no effect. It also does not show that placebo was better. A missing result is not equivalent to a negative result: the evidence needed to estimate a contrast is not available in the registry record.
The absence of analyses does not establish that every possible outcome was unmeasured or that no work took place; it establishes that analyses are not reported in the record. Similarly, the zero adverse-event counts alongside zero participants recorded at risk cannot support a conclusion about safety. The listed secondary outcomes do not provide findings about growth, neurodevelopment, respiratory status, vasoactive substances, or adverse effects.
General design features, including randomization and masking, can strengthen causal interpretation when implemented and paired with complete, appropriately analyzed data. They cannot compensate for an unavailable outcome dataset. Nor can planning calculations recover trial findings or demonstrate observed power. Any conclusion about effectiveness, safety, or the magnitude of a treatment effect would go beyond the information in the registry record.
12. Why This Trial Matters Statistically
This trial illustrates a distinction that matters in clinical research: a registered design is not the same as an interpretable result. The record specifies a randomized, quadruple-masked comparison and a physiological primary endpoint, but reports that the data needed to evaluate that endpoint were lost or destroyed. Without arm-level measurements and an analysis, the intended comparison cannot be estimated.
It also shows why uncertainty and missingness must be considered alongside study design. A trial can be carefully described yet still fail to yield an effect estimate if outcome data are unavailable. The listed enrollment of 9 does not reveal the amount of analyzable information, the balance between arms, or the precision that an analysis would have achieved. Those questions cannot be settled by design labels alone.
The distinction between missing evidence and evidence of no difference is especially important. No reported treatment contrast is not a result near zero, and zero entries in safety counts are not proof that no events occurred when the recorded number at risk is zero. Clear reporting of outcomes, analysis populations, uncertainty, and missing-data handling is essential for readers to evaluate a trial.
Finally, planning calculations should not be confused with evidence from participants. Sample-size illustrations can describe hypothetical requirements under assumptions, but they do not replace observed outcomes or supply an efficacy conclusion. In this record, the main statistical lesson is the limit imposed by unavailable data: the clinical question was defined, but its result cannot be assessed from the posted information.
13. 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 consequential limitation is explicit in the primary-outcome description: the study was terminated, and data were lost or destroyed after efforts to locate them were exhausted. No primary endpoint values, group summaries, effect estimate, measure of uncertainty, or analysis are reported. The treatment question therefore cannot be answered using the registry record.
The listed enrollment is 9, but the record does not specify allocation counts, the number treated, completion of follow-up, or the number with a final echocardiogram. It does not report participant characteristics, baseline pulmonary pressure, treatment adherence, or reasons for withdrawal. These omissions prevent assessment of the enrolled population and of the amount of information available for any intended comparison.
Several details needed to interpret the endpoint are absent: its unit, measurement procedure, summary measure, and analysis method. The primary outcome also includes several categories or time points and is not reduced to one comparison. The record does not explain the planned approach to those features, multiplicity, missing observations, or the analysis population.
The study status is TERMINATED, but the reason for termination is not reported in the registry record. The registry lists zero analyses and adverse-event entries with zero participants at risk; neither provides an outcome-based comparison. The listed secondary outcomes have no reported results. Together, these limitations mean that neither efficacy nor safety can be evaluated from the posted results.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Chronic Sildenafil for Severe Diaphragmatic Hernia — NCT00133679.
- Registry record last updated 2021-01-13; status last verified 2021-01.
- Results first posted 2021-01-13.
- 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.
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17. Record Summary
The registry record describes NCT00133679, “Chronic Sildenafil for Severe Diaphragmatic Hernia,” as a Phase 4 randomized, quadruple-masked, parallel-group study sponsored by the University of California, San Francisco. The listed enrollment is 9. The study compared sildenafil for 45 days with placebo for 45 days and was listed as TERMINATED.
The primary endpoint was estimated systolic pulmonary arterial pressure at the final echocardiogram, with a timeframe of 7 weeks. The registry states that the study was terminated and the data were lost or destroyed after efforts to locate them were exhausted. It lists six outcome measures and zero analyses. Secondary outcomes include vasoactive substances, adverse effects, growth, neurodevelopment, and respiratory status. No treatment-effect estimate or outcome analysis is reported in the registry record.