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 Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease (NCT00659529), a na phase 1, phase 2 study. The primary outcome is Change in Sputum Elastase Activity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00659529 |
| Phase | Phase 1, Phase 2 |
| Condition | Cystic Fibrosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Jewish Health |
| Results posted | Yes |
2. Clinical Question
Population
People with mild to moderate cystic fibrosis. The primary-outcome description focuses on participants who completed 6 weeks of sildenafil and had data before and after treatment.
Intervention
Oral sildenafil, administered three times per day during the study.
Comparator
No separate control group is listed. The study measures outcomes before treatment and at the end of the 6-week treatment period.
Primary question
Does sputum elastase activity change during sildenafil treatment, as an exploratory indicator of inflammation in cystic fibrosis lung disease?
The study’s stated purpose is to determine whether sildenafil can decrease inflammation in cystic fibrosis lung disease. Sputum elastase is the named primary measure, and the registry describes its analysis as exploratory. The endpoint description allows for either an increase or a decrease; the registry does not report a numerical result or direction of change.
The question is therefore about change during treatment in a single group, not about a difference between sildenafil and a concurrent untreated or placebo group. Without a control group, a change from baseline cannot by itself distinguish a treatment-associated change from changes over time, measurement variation, or other influences. The registry also lists change in exhaled breath condensate pH and change in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised as secondary outcomes. Their numerical results are not reported in the registry record.
3. Trial Design
This was a completed Phase 1 and Phase 2 study sponsored by National Jewish Health. The registry lists enrollment of 36 and dates from 2008-08 to primary completion in 2012-08. The intervention was sildenafil, and the study is described as a pilot study of systemic sildenafil administration to people with cystic fibrosis.
The design is listed as single group, with allocation recorded as NA and masking as none. All subjects were to receive oral sildenafil three times per day. Study endpoints were to be measured before the treatment period and at its end; the primary outcome specifies baseline and 6 weeks. No separate comparison arm is listed, so the design does not provide a concurrent control for interpreting changes over time.
The primary-outcome population is described as subjects who completed 6 weeks of sildenafil and had available data before and after treatment. The record also notes that one subject arrived at the final visit with 1 week of previously unreported symptoms consistent with pulmonary exacerbation, and that efficacy data were not analyzed for that subject. The end of the population description is incomplete, so further details about this exclusion are not reported in the registry record.
Although the registry lists enrollment of 36, the safety listing gives 27 as the number at risk for the open-label group. The record does not explain the relationship between those figures. The study’s single-group, unmasked structure is important when interpreting the outcomes: changes measured from baseline are descriptive of the group under study and do not establish what would have happened over the same period without sildenafil.
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 | Open-label (All Subjects) |
|---|---|
| STARTED | 36 |
| Received at least one dose of study drug | 27 |
| COMPLETED | 20 |
| NOT COMPLETED | 16 |
Reasons for not completing this period:
| Reason | Open-label (All Subjects) |
|---|---|
| Withdrawal by Subject | 4 |
| Protocol Violation | 3 |
| Screen failure | 9 |
Analysis population for the primary outcome, as defined in the registry: Subjects who completed 6 weeks of sildenafil and had available data for pre/post 6 weeks of sildenafil were analyzed. One subject presented to the final study visit with 1 week of previously unreported symptoms consistent with pulmonary exacerbation, and therefore, efficacy data was not analyzed on that subject as pre-specified in the protocol.
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: All patiens who received at least one dose of study drug.
| Characteristic | Unit | Open-label (All Subjects) |
|---|---|---|
| Participants analysed | 27 | |
| Age, Continuous | years | 25.7 (SD 5.5) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 11 |
| FEV1% predicted | % predicted | 77.5 (SD 19.6) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Sputum Elastase Activity, measured over Baseline and 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | micrograms/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in sputum elastase activity, measured in micrograms/mL, with baseline and 6 weeks identified as the measurement times. The registry describes the reported parameter as a mean and the dispersion as a 95% confidence interval. It calls the analysis exploratory and frames sputum elastase as a sputum biomarker of inflammation.
As a general statistical and biological rationale, a biomarker can provide an indicator of a biological process that may be relevant to a disease. Measuring the same outcome before and after treatment can describe whether the group’s average value changed over the treatment period. The endpoint description explicitly allows the measure to increase or decrease, so the direction and size of any change matter for interpreting the observed data.
A biomarker change is not, by itself, equivalent to a change in symptoms, lung function, or another patient-important outcome. The registry names additional outcomes, including exhaled breath condensate pH and the CFQ-R Respiratory Domain, but does not report their numerical results. Nor does it give the numerical mean change or confidence interval for sputum elastase activity. Consequently, the registry record does not establish the observed size, direction, or precision of the primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a relevant biological question: whether sputum elastase activity changes during a 6-week course of sildenafil in people with cystic fibrosis. However, it does not report the numerical primary-outcome estimate, its confidence interval, or a test result. The direction and magnitude of the measured change, and how precisely it was estimated, are therefore not reported in the registry record. No conclusion about the observed efficacy result can be drawn from the endpoint description alone.
The outcome is described as a mean with a 95% confidence interval. In general, the mean summarizes the group’s average measurement, while the confidence interval conveys uncertainty around an estimated value. A narrower interval indicates greater precision than a wider interval, but precision is not the same as evidence that an effect is clinically important. Since no estimate or interval is reported, neither the size of the change nor its precision can be assessed.
The design also affects interpretation. Measurements were planned before treatment and at its end, but there was no separate control group. A before-and-after change can be consistent with an effect of treatment, yet a single-group study cannot isolate treatment from other explanations for change over time. The open-label design also means masking was absent; the record does not describe safeguards that might address possible influences on measurement or reporting.
The registry lists enrollment of 36, while its open-label safety group lists 27 at risk. These are figures for different descriptions in the record, and no explanation of their relationship is reported. The efficacy population is further described as participants who completed treatment and had pre- and post-treatment data. This restriction means the primary analysis was not described as including every enrolled participant. The record notes one participant with symptoms consistent with pulmonary exacerbation at the final visit whose efficacy data were not analyzed, but does not provide a complete account of missing outcome data.
The secondary outcomes are named, but their results are not reported in the registry record. The registry lists three outcome measures and zero analyses. It does not report a multiplicity strategy, a statistical test, or an adjustment method. These omissions limit assessment of how outcomes were analyzed and how any positive or negative findings would have been interpreted across the set of outcomes. Overall, the registry description gives the study question and design but not the numerical efficacy findings needed to quantify the observed change.
9. Statistical Methods Explained
The primary outcome is continuous: sputum elastase activity is expressed in micrograms/mL, and the registry identifies the mean as the parameter of interest. A mean describes the average value in the analyzed group. For a change outcome, interpretation depends on the estimated change and its direction, as well as its uncertainty. The registry specifies a 95% confidence interval as the dispersion measure, but the numerical mean and interval are not reported in the registry record.
What does a confidence interval describe?
In general, a confidence interval is a range of values compatible with the data and the statistical procedure used to estimate uncertainty. It is not a guarantee that the true value lies within that particular interval, and it does not state the probability that a treatment works. Its width communicates precision: an interval that covers a broad range of plausible values is less precise than one covering a narrower range. Here, the registry names the interval type but gives no endpoints, so its width and the values it covers cannot be evaluated.
Confidence intervals also need to be read in relation to the outcome and study design. A confidence interval around an average change can characterize uncertainty about that group’s change, but it cannot create a missing control group. Even a precisely estimated before-and-after difference would not, on its own, separate treatment effects from other changes occurring over time. The registry does not give a clinically meaningful threshold for sputum elastase change, so the clinical importance of any possible estimate is not reported either.
Why does the single-group design matter?
In general, repeated measurements on the same participants are related: a participant’s value at baseline may be associated with that participant’s value at follow-up. An analysis of change should account for that pairing or use an appropriate model for repeated measurements. Treating related measurements as if they came from unrelated groups can misrepresent uncertainty. The registry identifies baseline and 6-week measurements, but the statistical method used to analyze them is not reported in the registry record. It is therefore not possible to determine how within-participant dependence was handled.
A single-group before-and-after comparison also lacks a concurrent estimate of change in the absence of treatment. Natural variation, changes in disease status, measurement conditions, or other influences could contribute to an observed shift. This is a general limitation of the design rather than a claim that any particular influence occurred in this study. Because masking was listed as none, the study was open-label. The registry does not describe whether outcome assessment was blinded or how laboratory measurement variability was addressed.
What can be learned from the analysis description?
The endpoint description calls the sputum biomarker analysis exploratory. An exploratory analysis can help characterize a possible signal and inform questions for later research, but its label does not supply a numerical result or a prespecified inferential procedure. The record lists three outcome measures and zero analyses. It does not report the test statistic, a p-value, an adjusted estimate, or a model specification. None of these should be inferred from the outcome name or the design.
In general, over-dispersion arises when observed variability is greater than a model assumes. If it is ignored in a setting where it is present, standard errors may be too small and confidence intervals too narrow. The registry does not report a model for these continuous measurements or any assessment of distributional assumptions, so there is no basis for saying whether over-dispersion was relevant to the primary analysis. For a continuous outcome, analysts may also examine the data’s distribution and the influence of unusual measurements; such procedures are not reported in the registry record.
How should planning calculations be understood?
The record’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. They depend on assumptions about the effect to detect. The stated planning setup is a hypothetical two-arm framework, whereas the registered trial is single group. The numerical planning results and a numerical observed effect are not reported in the registry record, so their implications cannot be assessed from these registry entries.
In general, sample-size planning asks how many participants per arm would be needed under specified assumptions; it does not retrospectively establish the strength of evidence in a completed study. Planning for a fraction of an observed effect is especially dependent on the effect estimate used, which can be unstable in a small pilot study. No numerical planning estimates are included in the registry record summarized by these registry entries. The planning assumptions should therefore be kept separate from the trial’s observed outcome evidence, which is not numerically reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies three outcome measures: change in sputum elastase activity as the primary outcome, and changes in exhaled breath condensate pH and the CFQ-R Respiratory Domain as secondary outcomes. It lists zero analyses. The numerical results for these outcomes and any statistical tests are not reported in the registry record.
When a study assesses multiple outcomes, general statistical practice distinguishes the primary question from additional outcomes and considers how repeated testing affects interpretation. A multiplicity plan may specify which outcomes are confirmatory, whether tests are adjusted, and how secondary findings are treated. No such plan or adjustment is reported in the registry record. Without it, readers cannot determine whether or how the chance of false-positive findings across outcomes was addressed. The outcomes’ stated labels alone do not establish a testing hierarchy or a correction method.
The primary efficacy population is described as participants who completed 6 weeks of sildenafil and had available measurements before and after treatment. The record notes one participant with symptoms consistent with pulmonary exacerbation at the final visit, whose efficacy data were not analyzed. The population description ends before its final detail is complete. Other missing-data rules, the amount of missing data for each outcome, and methods for handling missing measurements are not reported in the registry record.
As a general matter, restricting analysis to participants with complete measurements can affect the result if those with missing data differ from those analyzed. Whether that concern applies, and in which direction, cannot be assessed without fuller information. The registry does not report an intention-to-treat analysis, imputation, sensitivity analysis, or a rationale for any missing-data assumption. The stated eligibility for the efficacy analysis and the single noted exclusion are not enough to characterize the full analysis population or the potential impact of missing data.
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 |
|---|---|---|---|
| Open-label (All Subjects) | 2 | 27 | 7.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Open-label (All Subjects) | 0 of 27 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Open-label (All Subjects) | 24 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Open-label (All Subjects) |
|---|---|---|
| CF pulmonary exacerbation | Respiratory, thoracic and mediastinal disorders | 2 of 27 |
| Distal Intestinal Obstruction Syndrome | Gastrointestinal disorders | 1 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Open-label (All Subjects) |
|---|---|---|
| rhinorhhea/congestion | Respiratory, thoracic and mediastinal disorders | 9 of 27 |
| headache | Nervous system disorders | 6 of 27 |
| Sore throat/throat clearing | General disorders | 6 of 27 |
| Increased cough | Respiratory, thoracic and mediastinal disorders | 6 of 27 |
| Flushing | General disorders | 5 of 27 |
| dyspepsia | Gastrointestinal disorders | 4 of 27 |
| myalgia | Musculoskeletal and connective tissue disorders | 4 of 27 |
| Increased/thicker sputum | Respiratory, thoracic and mediastinal disorders | 4 of 27 |
| Insomnia | General disorders | 3 of 27 |
| Chest tigntness/congestion | Respiratory, thoracic and mediastinal disorders | 2 of 27 |
Serious events with the highest arm-level rate: cf pulmonary exacerbation (7.4%), distal intestinal obstruction syndrome (3.7%).
The open-label safety listing gives 27 as the number at risk. It lists 2 as affected by serious adverse events, 24 as affected by other adverse events, and 0 deaths. These are the safety figures recorded for the group; the registry does not provide a comparative control-group rate. The enrollment figure of 36 is separate, and the registry does not explain why the safety group’s at-risk figure differs.
The serious-event terms listed include CF pulmonary exacerbation at 7.4% and Distal Intestinal Obstruction Syndrome at 3.7%. These percentages are reproduced as reported. The registry does not provide further details in the registry record about event timing, duration, recurrence, severity beyond the serious-event classification, or attribution to sildenafil. The listed terms should not be interpreted as proof that sildenafil caused those events, nor does the absence of a listed death establish the absence of other safety concerns.
In general, a safety count describes events recorded within the stated group and observation context; it does not by itself establish comparative risk. With no separate control group, these figures cannot quantify how event occurrence differed from what would have happened without treatment. The registry record does not report additional details needed to assess the completeness of adverse-event capture or the basis for classifying events as related or unrelated to treatment.
12. What the Result Does, and Does Not, Mean
The record establishes that the study examined oral sildenafil in a single group of people with mild to moderate cystic fibrosis, with sputum elastase activity designated as the exploratory primary outcome. It also documents a plan to measure outcomes before treatment and at the end of 6 weeks. These details define the research question and the setting in which change was to be assessed.
The record does not report the numerical primary-outcome result, its confidence interval, or a statistical test. It therefore does not show whether sputum elastase activity increased or decreased, how large any change was, or how precisely it was estimated. The secondary outcome results are also not reported in the registry record. The stated purpose of investigating inflammation should not be confused with evidence of an observed reduction in inflammation.
Even if a numerical before-and-after change were available, the single-group design would not by itself demonstrate that sildenafil caused that change. A concurrent comparison group would help distinguish changes associated with treatment from changes that may occur over time or from other influences. The unmasked design is another consideration, although the record does not report how outcome assessment was conducted.
The safety listing records serious and other adverse events and no deaths in the stated safety group. Those descriptive figures do not establish comparative safety or attribution to treatment. They also do not resolve why the registry gives an enrollment figure of 36 and a safety at-risk figure of 27.
Overall, the registry record supports a description of the trial’s purpose, design, outcomes, and selected safety figures. It does not support a quantitative conclusion about the primary endpoint or a causal conclusion about efficacy. The missing outcome estimates, analysis details, and fuller account of the analysis population limit what can be inferred from the registry information.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its central question is framed around change in a continuous biomarker, while its design is single group and open label. A baseline measurement and a follow-up measurement can describe change, but that structure does not provide a concurrent estimate of the change that would occur without treatment. The distinction between describing change and attributing change to an intervention is fundamental to interpreting clinical research.
The endpoint is reported as a mean with a 95% confidence interval. This makes precision part of the intended summary, not just the direction of the result. Yet the registry does not report the mean change or its interval. The case illustrates why an outcome’s name and analysis description are not substitutes for the estimate itself: without the numerical result, neither effect size nor precision can be evaluated.
The trial also makes the analysis population important. The primary description focuses on participants who completed treatment and had measurements at both time points, and it notes one participant whose efficacy data were not analyzed after symptoms consistent with pulmonary exacerbation. The record does not give a complete missing-data account. These details matter because the group analyzed may not fully represent everyone who entered a study, and the reasons for absent measurements can affect interpretation.
Finally, the registry names a primary measure and secondary outcomes but does not report analyses or a multiplicity plan. In general, a clearly specified outcome hierarchy and transparent analysis methods help readers distinguish confirmatory questions from exploratory ones. Here, the registry’s description supports the conclusion that the sputum biomarker analysis was exploratory, while leaving the numerical findings and inferential procedures unreported. The study is therefore a useful example of why design, analysis population, precision, and completeness of reporting must be considered together.
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 immediate limitation of the available registry record is that it gives no numerical efficacy estimate for the primary endpoint. Although it identifies the mean and a 95% confidence interval as the summary, neither the mean change nor the interval values are reported. The direction, magnitude, and precision of the primary result are therefore unknown from this record. Numerical results for the named secondary outcomes are also not reported.
The single-group design has no concurrent comparator, and masking is listed as none. A change from baseline can be described, but the design cannot isolate a treatment effect from other sources of change over time. The registry does not report details of outcome assessment or laboratory procedures that would help readers evaluate measurement reliability.
The primary population is restricted to participants who completed 6 weeks and had available measurements before and after treatment. One participant with symptoms consistent with pulmonary exacerbation at the final visit is noted as having efficacy data that were not analyzed. The population description is incomplete, and other missing-data methods and analysis populations are not reported in the registry record. The relationship between the enrollment figure of 36 and the safety at-risk figure of 27 is also not explained.
The record identifies three outcome measures and zero analyses, but does not report statistical tests, model details, a multiplicity approach, or numerical confidence intervals. It also does not give a clinically meaningful threshold for the biomarker. These limitations prevent a full assessment of the strength, precision, and clinical relevance of the efficacy findings. The safety information is descriptive and does not include a control group for comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease — NCT00659529.
- Registry record last updated 2026-05-14; status last verified 2026-05.
- Results first posted 2014-05-02.
- 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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18. Record Summary
NCT00659529 is a completed Phase 1 and Phase 2, open-label, single-group pilot study sponsored by National Jewish Health. It lists enrollment of 36 and dates from 2008-08 to primary completion in 2012-08. Participants with mild to moderate cystic fibrosis were to receive oral sildenafil three times per day.
The primary outcome was change in sputum elastase activity from baseline to 6 weeks, described as an exploratory mean with a 95% confidence interval. The registry lists two secondary outcomes: change in exhaled breath condensate pH and change in the CFQ-R Respiratory Domain. Numerical efficacy results and analysis methods are not reported in the registry record. The safety listing gives 27 at risk, 2 affected by serious adverse events, 24 affected by other adverse events, and 0 deaths. The record does not provide a concurrent control group or explain the difference between the enrollment and safety-group figures.