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 Sildenafil Exercise: Role of PDE5 Inhibition (NCT04039087), a randomized phase 2, phase 3 study. The primary outcome is 6 Minute Walk Distance (6MWD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04039087 |
| Phase | Phase 2, Phase 3 |
| Condition | Cystic Fibrosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 31 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Jewish Health |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns people with cystic fibrosis. The registry record reports an enrollment of 31, with 15 participants in the sildenafil outcome group and 16 in the placebo outcome group. Further eligibility details and participant characteristics are not reported in the registry record.
Intervention
The active intervention was sildenafil 40 mg by mouth three times per day. The registry record describes the intervention as an oral capsule and identifies the dose and frequency in the arm description.
Comparator
The comparison group received a placebo oral capsule three times per day. The registry record does not describe other care or co-interventions for either group.
Primary question
The primary outcome was change in six-minute walk distance, measured in meters, between week 1 and week 13. The clinical question is whether the observed mean change in walking distance differed between the randomized sildenafil and placebo groups. The posted results provide a mean change and 95% confidence interval for each group, but do not report a between-group estimate or inferential test. They therefore describe the arm-level outcomes, rather than directly quantifying the uncertainty around a treatment-versus-placebo contrast.
3. Trial Design
This completed study is registered as a randomized, quadruple-masked, parallel-group trial with phase designations of PHASE2 and PHASE3. It was sponsored by National Jewish Health and studied cystic fibrosis. The registry record lists an enrollment of 31. The primary completion date is 2024-06-30, and the study status is COMPLETED.
Participants were assigned to sildenafil or placebo. The sildenafil arm is described as receiving sildenafil 40 mg by mouth three times per day; the placebo arm is described as receiving placebo three times per day. The registry identifies the allocation as randomized and the masking as quadruple, but does not describe the allocation ratio, sequence-generation method, concealment procedure, or which specific groups of people were masked.
The primary outcome was six-minute walk distance (6MWD), in meters, with the stated timeframe being change in distance walked between week 1 and week 13. The registry also lists the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score as a secondary outcome. Details of its results are not included in the posted outcome values described in the registry record.
The primary outcome groups include 15 participants assigned to sildenafil and 16 assigned to placebo. These are the group sizes attached to the posted outcome summaries; the analysis population and the number of participants with outcome data at each assessment are not reported in the registry record. A sample-size justification, detailed protocol, and prespecified statistical analysis plan are not reported in the registry record.
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 Arm |
|---|---|---|
| STARTED | 15 | 16 |
| COMPLETED | 11 | 15 |
| NOT COMPLETED | 4 | 1 |
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.
| Characteristic | Unit | Sildenafil | Placebo Arm | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 16 | 31 | |
| Age, Continuous | Years | 32.2 (SD 11.7) | 32.0 (SD 9.2) | 32.1 (SD 10.3) |
| Sex: Female, Male: Female | Participants | 8 | 6 | 14 |
| Sex: Female, Male: Male | Participants | 7 | 10 | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): White | Participants | 13 | 12 | 25 |
| Race (NIH/OMB): More than one race | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 15 | 28 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as 6 Minute Walk Distance (6MWD), measured over Change in distance walked between week 1 and week 13.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Meters (m) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in six-minute walk distance from week 1 to week 13, measured in meters. The six-minute walk test records the distance a participant walks during a specified six-minute period. The registry describes exercise capacity as an objective measure of exercise tolerance and gives the rationale that exercise capacity predicts mortality in people with cystic fibrosis. The endpoint therefore represents walking performance over the stated study interval, rather than a direct measure of vascular function or a measure of long-term survival.
The posted outcome is expressed as a mean change for each arm, accompanied by a 95% confidence interval. The sildenafil group had a mean change of -4.0 meters, with a 95% confidence interval from -32.0 to 25.0. The placebo group had a mean change of 27.0 meters, with a 95% confidence interval from 2.0 to 52.0. These are arm-specific summaries. They do not themselves give the estimated difference between groups.
The endpoint’s stated timeframe identifies the two assessment points used for the change. Further information about how the walk test was conducted, how repeated or incomplete assessments were handled, and whether the analysis adjusted for baseline distance is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted results describe mean change in six-minute walk distance separately for the two randomized groups. For sildenafil, the mean change was -4.0 meters, with a 95% confidence interval from -32.0 to 25.0. For placebo, the mean change was 27.0 meters, with a 95% confidence interval from 2.0 to 52.0. The confidence intervals communicate uncertainty around each arm’s mean; they are not confidence intervals for the difference between the arms.
These values should be read as estimates from the enrolled groups, not as definitive statements about what would occur in all people with cystic fibrosis. The registry record does not report an estimate of the between-group difference, its confidence interval, or a p-value for the primary endpoint. Without those quantities, the posted arm-level summaries do not establish the size or statistical uncertainty of a treatment-versus-placebo contrast. No conclusion about statistical significance of that contrast can be drawn from an unreported test.
The interval for the sildenafil arm includes values on both sides of zero, whereas the placebo interval ranges from 2.0 to 52.0. This describes the stated uncertainty around each group’s mean change; it does not substitute for a direct comparison. A comparison should account for uncertainty in both groups and should use the trial’s prespecified analysis, if available. That analysis is not reported in the registry record.
The outcome groups contain 15 and 16 participants, respectively. These group sizes give important context for the precision of the estimates. The intervals are broad, particularly for the sildenafil estimate, indicating that a range of mean changes is compatible with the arm-level summary. The registry does not report individual participant data, standard deviations, baseline values, or a model-based analysis that could provide further context.
In short, the posted data show a mean decrease in the sildenafil group and a mean increase in the placebo group over the stated interval. They do not report the randomized contrast needed to quantify how different those changes are, nor a statistical test of that contrast. This is a description of the posted outcome summaries, not evidence for or against a clinical benefit.
9. Statistical Methods Explained
What do the reported means describe?
Six-minute walk distance is a continuous outcome because it can take a range of measured values. The registry reports the mean change for each arm. A mean is a measure of the center of the observed values: it summarizes the group’s average change, while not showing how much participants differed from one another. The reported means are -4.0 meters for sildenafil and 27.0 meters for placebo. These values are changes between the stated week 1 and week 13 assessments, not the groups’ absolute walking distances at either assessment.
What does a 95% confidence interval mean?
General statistical explanation: a confidence interval expresses uncertainty in an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision than a wider interval, all else equal. It does not mean that 95% of participants’ individual changes fall inside the interval, and it does not show the range of individual responses. The registry reports a 95% confidence interval of -32.0 to 25.0 for the sildenafil mean and 2.0 to 52.0 for the placebo mean. The method used to calculate these intervals is not reported in the registry record.
Why is a direct contrast important?
For a randomized two-arm trial, the treatment question concerns the difference between the groups, not whether either group’s mean change is considered in isolation. A direct contrast estimates how far apart the arm outcomes are and quantifies uncertainty around that comparison. The registry record posts arm-level means and intervals but does not report a between-group estimate, its confidence interval, or a p-value. A reader should not treat either arm’s interval as if it were an interval for the treatment contrast, or infer a formal comparison from the arm summaries alone.
General statistical explanation: a p-value, when reported, measures how compatible the observed data are with a specified null model, given the analysis assumptions. It does not measure the probability that a treatment works, and it does not describe the magnitude or clinical importance of an effect. No primary-outcome p-value or null hypothesis is reported in the registry record, so no such interpretation is available for this outcome.
What can be said about precision?
The group sizes attached to the primary outcome are 15 for sildenafil and 16 for placebo. The confidence intervals provide the registry’s displayed uncertainty around the arm means. The individual-level variability and the exact interval calculation are not reported in the registry record, so further reconstruction of precision is not warranted. The interval widths also should not be confused with a clinically important difference: a threshold for clinical importance is not reported in the registry record.
What do the planning assumptions mean?
General statistical explanation: sample-size planning asks how many participants would be needed under stated assumptions to detect a chosen effect with a chosen probability of rejecting a null hypothesis. A planning illustration based on an observed effect is not the same as the trial’s original design justification, and it is not observed power. The planning assumptions associated with this analysis specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. No numerical planning counts are reported in the registry record. The registry record does not report the trial’s own sample-size justification, the target effect used at design, or the assumptions used by the investigators.
How should the statistical method be assessed?
The randomized parallel-group design supports a comparison between assigned groups, but the posted arm summaries alone do not reveal the statistical model or analysis population used. It is not reported in the registry record whether the main analysis followed assigned treatment, included only participants who completed both visits, adjusted for baseline 6MWD, or used another approach. These are potentially consequential choices, especially when the outcome is a change score and follow-up measurements may be unavailable. The registry record does not describe the estimation method, standard-error calculation, or handling of missing measurements.
General statistical explanation: methods for continuous outcomes commonly rely on assumptions about the distribution of measurements or model residuals. With small groups, estimates can be sensitive to individual observations and to departures from those assumptions. The registry does not report diagnostic checks or sensitivity analyses for this endpoint. It is therefore appropriate to keep interpretation at the level of the displayed summaries and avoid attributing an unreported model or test to the trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score as a secondary outcome and reports two outcome measures in total. It does not report an approach for controlling multiplicity across outcomes, time points, or analyses. A multiplicity plan is not reported in the registry record, so it is unclear whether the primary outcome was intended to be interpreted as one of several confirmatory tests or whether secondary outcomes were exploratory.
The registry record reports zero analyses in the analysis listing. It does not provide a primary-outcome between-group estimate, p-value, or description of a statistical analysis plan. The specific analysis population, handling of participants with missing week 1 or week 13 measurements, and method for missing data are not reported in the registry record. The posted outcome group sizes do not by themselves establish that all randomized participants contributed data at both assessments.
General statistical explanation: missing outcome data can affect both precision and validity, particularly if the likelihood of missingness is related to participants’ outcomes or treatment assignment. Different assumptions and methods can yield different results. Without the number and pattern of missing measurements, the analysis approach, and relevant sensitivity analyses, the effect of missing data cannot be assessed from these registry results. No imputation method, complete-case rule, or other missing-data procedure should be assumed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sildenafil | 1 | 15 | 6.7% |
| Placebo Arm | 0 | 16 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sildenafil | 0 of 15 |
| Placebo Arm | 0 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sildenafil | 6 of 15 |
| Placebo Arm | 6 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | Sildenafil | Placebo Arm |
|---|---|---|---|
| Pulmonary Exacerbation | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 0 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sildenafil | Placebo Arm |
|---|---|---|---|
| Rhinitis | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 3 of 16 |
| Headache | Nervous system disorders | 0 of 15 | 2 of 16 |
| Flushing | Nervous system disorders | 0 of 15 | 2 of 16 |
| Body Aches | Nervous system disorders | 1 of 15 | 1 of 16 |
| Sinusitis | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 0 of 16 |
| Wheezing | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 0 of 16 |
| Chest tightness | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 16 |
| Chest congestion | Respiratory, thoracic and mediastinal disorders | 0 of 15 | 2 of 16 |
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 16 |
| Hoarse Voice | Respiratory, thoracic and mediastinal disorders | 2 of 15 | 0 of 16 |
Serious events with the highest arm-level rate: pulmonary exacerbation (6.7%).
The registry reports serious adverse events for 1 of 15 participants in the sildenafil group and 0 of 16 participants in the placebo group. It reports other adverse events for 6 of 15 participants in each group. Deaths are reported as 0 in both groups. The listed top serious adverse event term is Pulmonary Exacerbation, with 6.7% shown in the registry record.
These counts are descriptive. The registry does not report a comparative safety estimate or statistical test, and the small group counts limit how precisely differences in uncommon events can be assessed. The adverse-event summaries do not establish that an event was caused by the assigned intervention. The registry record does not report event-level narratives, severity details beyond the serious-event classification, exposure-adjusted rates, or the rules used to collect and classify events. The figures should therefore be read as posted counts within the two groups, not as proof of comparative safety or of causation.
12. What the Result Does, and Does Not, Mean
The primary outcome summaries show different arm-level patterns over the interval from week 1 to week 13: the sildenafil group’s mean change was -4.0 meters, and the placebo group’s mean change was 27.0 meters. Their 95% confidence intervals describe uncertainty around those separate means. The registry does not report a direct estimate of the difference between groups or a statistical test of the primary comparison.
That distinction limits what the posted results can establish. Randomization is intended to support a comparison of assigned groups, but an arm-by-arm display does not itself quantify the treatment contrast or its precision. The interval around one group’s mean cannot be used as the interval around the difference. A reader should not infer that the treatment effect is statistically significant or not statistically significant when the relevant contrast and test are not reported.
The registry describes exercise capacity as an objective measure of exercise tolerance and gives a rationale involving vascular dysfunction and sildenafil. The posted primary endpoint, however, is walking distance, not a direct measure of vascular function. The results presented do not establish a mechanism, explain why the arm means differ, or report the secondary quality-of-life outcome. The trial’s posted results also do not establish longer-term outcomes.
General statistical explanation: estimates from a trial are subject to sampling uncertainty, and the interpretation of a result depends on its design, analysis, completeness, and clinical context. Here, the registry does not report the full analysis plan, participant-level outcome data, missing-data handling, or a threshold for a clinically important change. Those omissions limit the assessment of precision and robustness. The appropriate conclusion is confined to the descriptive arm-level outcome and adverse-event summaries reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between reporting outcomes by arm and estimating a randomized treatment contrast. The registry provides mean changes and confidence intervals for both groups, which communicate the observed arm-level pattern and uncertainty around each mean. The primary clinical comparison, however, requires an estimate and uncertainty measure for the difference between assigned groups. Those are not reported in the registry record.
The distinction is important because an arm’s change from its own baseline is not the same quantity as the difference in change between treatment groups. In a randomized study, the comparison between groups is the relevant basis for estimating an intervention effect. Reporting only group means leaves the reader without the direct contrast, its precision, or a formal test. It also prevents a clear assessment of whether the observed pattern is compatible with a broad range of between-group effects.
The small outcome groups and the width of the displayed intervals are also relevant to precision. General statistical explanation: estimates based on limited information can be uncertain, and additional sample-size planning does not retroactively increase the information in the observed trial. Any planning illustration based on the observed effect should be understood as a hypothetical design exercise under its stated assumptions, not as evidence that the study had a particular probability of detecting an effect.
Finally, registry reporting is part of statistical transparency. Information about the analysis population, missing outcomes, multiplicity, and the prespecified model would help readers assess whether the posted summaries answer the original trial question. These details are not reported in the registry record. The case therefore illustrates why outcome estimates, confidence intervals, and analysis methods should be presented for the comparison that the randomized design was intended to address.
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 posted primary results are limited to arm-level means and 95% confidence intervals. The registry does not report a between-group contrast, its confidence interval, or a p-value. Consequently, the magnitude and precision of the randomized comparison cannot be evaluated from these summaries alone.
The registry does not report baseline 6MWD values, individual participant results, standard deviations, or the method used to calculate the confidence intervals. It also does not describe the number of participants with measurements at each visit or how missing outcomes were handled. These omissions make it difficult to assess the analysis population and the robustness of the change estimates.
Eligibility criteria, participant characteristics, intervention adherence, and details of the walk-test procedure are not reported in the registry record. The registered masking category is quadruple, but the specific masked groups and implementation details are not described. The allocation ratio and randomization procedures are also not reported.
The registry lists one secondary outcome, the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score, but does not include its result in the posted outcome values. The multiplicity strategy, prespecified analysis plan, and trial-specific sample-size justification are not reported in the registry record. These limitations concern what can be assessed from the registry reporting; they do not establish that the investigators did or did not use any particular procedure.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sildenafil Exercise: Role of PDE5 Inhibition — NCT04039087.
- Registry record last updated 2026-08-28; status last verified 2026-07.
- Results first posted 2026-08-28.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed randomized, quadruple-masked, parallel-group trial sponsored by National Jewish Health, with phase designations of PHASE2 and PHASE3 and enrollment of 31. Participants were assigned to sildenafil 40 mg by mouth three times per day or placebo three times per day. The primary outcome was change in six-minute walk distance between week 1 and week 13.
The posted mean change was -4.0 meters for sildenafil, with a 95% confidence interval from -32.0 to 25.0, and 27.0 meters for placebo, with a 95% confidence interval from 2.0 to 52.0. The registry record does not report a between-group estimate or test. Serious adverse events were reported for 1 of 15 sildenafil participants and 0 of 16 placebo participants; other adverse events were reported for 6 participants in each group, with 0 deaths in either group.