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 for Chronic Obstructive Pulmonary Disease (NCT00104637), a randomized phase 2 study. The primary outcome is 6 Minute Walk Distance.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00104637 |
| Phase | Phase 2 |
| Condition | Pulmonary Disease, Chronic Obstructive, Emphysema |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 10 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Kawut, Steven, MD |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes patients with chronic obstructive pulmonary disease and lists emphysema as a condition. Ten participants were enrolled. The primary outcome record does not further describe the population, and specific eligibility criteria or baseline characteristics are not reported in the registry record.
Intervention
The intervention was sildenafil citrate. The crossover sequences describe sildenafil followed by washout and placebo, or placebo followed by washout and sildenafil. The recorded purpose was to examine exercise capacity and lung function.
Comparator
The comparator was placebo. The registry describes a randomized, triple-masked crossover study. The detailed masking procedures, including which study roles were masked, are not reported in the registry record.
Primary question
The primary outcome was 6 Minute Walk Distance, measured in meters. The question was whether the distance walked within six minutes differed during the sildenafil and placebo treatment periods. The posted estimates are 458.2 meters for sildenafil and 466.1 meters for placebo, each with a 95% confidence interval. A comparative effect estimate and its inferential test are not reported in the registry record.
3. Trial Design
This was a phase 2, randomized, triple-masked, placebo-controlled crossover study of sildenafil for chronic obstructive pulmonary disease. The record lists 10 participants as enrolled and marks the study completed. The recorded start was 2005-02, and primary completion was 2008-11.
In a crossover design, participants receive more than one assigned treatment in sequence, rather than remaining in a single treatment group throughout. The registry lists two sequences: sildenafil first, followed by washout, then placebo; and placebo first, followed by washout, then sildenafil. This design can allow each participant to contribute information under both treatments, so comparisons may account for the paired nature of the measurements. Whether the posted outcome values use paired participant-level data is not reported in the registry record.
The washout is part of each sequence, but the washout duration and the rationale for its length are not reported in the registry record. Details of randomization generation, concealment, masking procedures, and how sequence assignment was implemented are also not reported in the registry record. The record does not state whether period or carryover effects were assessed or how they were handled analytically.
The primary outcome timeframe is Period 1 and Period 3, within 8 weeks. The outcome is the distance walked during a six-minute walk. Although the study also lists lung-function and other secondary outcomes, the registry record does not post analyses for those measures. The posted primary outcome includes 10 participants for sildenafil and 9 for placebo. Why the number contributing to the placebo estimate differs from the enrollment count is 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.
Period 1: ( TREATMENT: 4 Weeks)
| Stage | Sildenafil /Placebo | Placebo /Sildenafil |
|---|---|---|
| STARTED | 6 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Sildenafil /Placebo | Placebo /Sildenafil |
|---|---|---|
| Adverse Event | 1 | 0 |
Period 2 (WASHOUT: 1 Week)
| Stage | Sildenafil /Placebo | Placebo /Sildenafil |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
Period 3 ( TREATMENT: 4 Weeks)
| Stage | Sildenafil /Placebo | Placebo /Sildenafil |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 0 | 0 |
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 | Randomized Participants |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 |
| Age, Categorical: >=65 years | Participants | 3 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 8 |
| Region of Enrollment: United States | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as 6 Minute Walk Distance, measured over Period 1 and Period 3 ( within 8 weeks).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | meters |
| Endpoint classification | Continuous Endpoint |
6 Minute Walk Distance is the distance a participant walks during a six-minute walk test, recorded in meters. It is a continuous measure: its values can vary across a range, rather than falling into only categories such as improved or not improved. The registry identifies the primary outcome as a least-squares mean and gives a 95% confidence interval for each posted treatment estimate.
As a general matter, a walking-distance measure can describe exercise capacity in a standardized task. Measuring distance over a fixed test duration gives a quantitative outcome that can be compared across treatment periods. It does not, by itself, explain why a participant walked a particular distance or establish whether any observed change is important to participants.
The registry states that the distance walked within six minutes was measured and documented, with the timeframe identified as Period 1 and Period 3, within 8 weeks. It does not report the test administration details, such as the setting, encouragement procedures, or rules for handling an interrupted test. Those details can affect how consistently a functional outcome is measured, so their absence limits assessment of measurement procedures.
The posted treatment estimates are 458.2 meters for sildenafil and 466.1 meters for placebo. The confidence intervals describe uncertainty around those estimates; they are not themselves a treatment-versus-placebo estimate. The registry record does not report a direct contrast for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted least-squares mean for 6 Minute Walk Distance is 458.2 meters for sildenafil, with a 95% confidence interval from 380.0 to 536.0. For placebo, the estimate is 466.1 meters, with a 95% confidence interval from 388.0 to 544.0. The outcome record lists 10 participants for sildenafil and 9 for placebo. These are treatment-specific estimates, not a reported paired difference between treatments.
A confidence interval communicates the statistical uncertainty around an estimate under the analysis used. In general, a wider interval indicates less precision than a narrower interval. The reported intervals cover a broad range of distances, so the treatment-specific mean estimates are not highly precise. The registry record does not explain how the least-squares means or their intervals were calculated, and it does not provide the model specification needed to assess that uncertainty in detail.
The presence of intervals for each treatment does not provide the uncertainty for the contrast of interest. A crossover comparison would ordinarily use the relationship between each participant's measurements under the two treatments, along with any relevant period or sequence information. Separate means and intervals do not show that within-participant relationship. It is therefore not possible to derive a valid comparative confidence interval or test from these summaries alone. The registry record does not report a primary treatment contrast, p-value, or analysis result.
The record lists 10 participants enrolled, while the primary-outcome estimates include 10 for sildenafil and 9 for placebo. The reason for this difference, and whether missing outcome data occurred, are not reported in the registry record. In a crossover study, an outcome may be available for one treatment period but not another; without participant-level information and an account of missingness, the implications for the comparison cannot be established.
These results should be read as estimates of walking distance under the two recorded treatment conditions, with substantial uncertainty around each estimate. They do not establish the size or precision of a treatment contrast. Nor do they establish that one treatment is superior or equivalent: such conclusions require a clearly reported comparison and analysis. The posted values are descriptive evidence from a small completed study, and they do not support a treatment recommendation.
9. Statistical Methods Explained
The registry identifies the primary outcome summary as a least-squares mean with a 95% confidence interval. These labels describe the type of summary, but the statistical model and the treatment contrast are not reported in the registry record. The distinction matters: a treatment-specific mean is not the same quantity as a difference between treatments.
What does a least-squares mean represent?
As a general statistical concept, a least-squares mean is a model-based mean, sometimes called an adjusted mean. It is estimated from a statistical model rather than necessarily being the simple arithmetic average of the observed values. Depending on the model, it can account for design features or covariates. The term alone does not identify which adjustments were made. For this study, the covariates, model terms, estimation method, and assumptions behind the least-squares means are not reported in the registry record. It is therefore not possible to determine from the label whether the estimates account for participant pairing, treatment sequence, study period, or other factors.
How should the confidence intervals be read?
In general, a confidence interval expresses the uncertainty associated with an estimate under a specified statistical procedure. A 95% confidence procedure is designed so that, over repeated comparable studies and under its assumptions, intervals constructed in that way would cover the underlying quantity at the stated rate. It is not a direct probability statement that a particular fixed quantity lies within this particular interval. The registry reports intervals of 380.0 to 536.0 meters for sildenafil and 388.0 to 544.0 meters for placebo. Those intervals pertain to the separate treatment estimates as reported; they are not a confidence interval for the difference between treatments.
Comparing two separate confidence intervals is not a substitute for estimating a treatment contrast. The uncertainty of a contrast depends on the uncertainty in each estimate and on their covariance. In a crossover study, measurements from the same participant under different treatments can be correlated. A paired analysis can use that correlation, while an analysis that treats the measurements as independent may not represent the design appropriately. The registry does not state how this dependence was handled. The intervals alone do not reveal it.
Why does the crossover structure matter?
As a general matter, crossover studies compare treatment periods within participants, which can reduce variation due to stable differences between participants when the analysis uses the pairing appropriately. However, outcomes may also vary by period, and an effect of the first treatment could persist into a later period. The sequence includes a washout, but its duration and the analysis of possible carryover are not reported in the registry record. The record also does not state whether treatment, period, or sequence effects were included in the model. These details are important for understanding how the estimates relate to the randomized crossover comparison.
The outcome timeframe identifies Period 1 and Period 3, within 8 weeks. That description identifies the periods associated with measurement, but it does not specify the model, the exact analysis population, or how any unavailable period measurements were handled. A complete methods account would clarify which participants and measurements contributed to each estimate and how the paired structure was used.
What can be concluded from the posted summaries?
The summaries support a description of the treatment-specific estimates and their uncertainty. They do not report a direct estimate of the sildenafil-versus-placebo contrast, a hypothesis test, or a p-value. The registry lists 0 analyses. The reason no analysis results are listed, and whether analyses were conducted outside the registry record, are not reported in the registry record. Consequently, the central inferential question cannot be answered from these summary statistics.
The record labels the outcome measure as continuous. For continuous outcomes, statistical analysis often focuses on a difference in means or a model-based treatment contrast, with uncertainty expressed using a confidence interval. Those are general practices, not a claim about what this study did. The analysis plan, model specification, assumptions, and exact contrast are not reported in the registry record. In particular, no unadjusted recalculation of a contrast is presented in the posted results, and no comparative estimate can be recovered reliably without information on the within-participant data and covariance.
The listed planning illustrations are based on the observed effect and stated assumptions, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are hypothetical planning calculations, not observed power and not evidence that the original study had a particular design justification. The protocol's sample-size justification and the method used to plan enrollment are not reported in the registry record. Because the posted primary outcome does not include a treatment contrast, the interpretation of any planning illustration should remain conditional on its stated assumptions rather than being treated as a trial finding.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 9 posted secondary outcomes, including forced vital capacity, forced expiratory volume in the first second, dyspnea score at the end of the six-minute walk test, diffusing capacity, arterial blood gas measures, the A-a gradient, and oxygen pulse. The registry lists 0 analyses. Results for these secondary measures are not reported in the registry record.
When a study examines multiple outcomes, tests, time points, or subgroups, the chance of at least one apparently notable result can increase if each is interpreted separately. As a general statistical principle, multiplicity may be addressed through a prespecified hierarchy, adjustment procedures, or careful designation of outcomes as exploratory. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether any adjustment was used. It also does not report interim analyses or stopping rules; these should not be inferred from the completed status.
The primary outcome is identified, but the registry record does not describe a statistical analysis plan or explain how the primary and secondary outcomes were to be analyzed together. Without that information, it is not possible to tell whether the posted estimates represent the planned primary analysis or how secondary findings would have been interpreted in relation to it.
The primary outcome includes 10 participants for sildenafil and 9 for placebo, compared with 10 enrolled. The reason for the different counts is not reported in the registry record. The record does not specify whether outcome data were missing, whether any participant withdrew, what analysis population was intended, or how missing measurements were handled. No imputation method or sensitivity analysis is reported. In a crossover design, missingness in one treatment period can affect the available paired comparison; the registry does not explain whether such a comparison was conducted.
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 | 0 | 10 | 0.0% |
| Placebo | 0 | 9 | 0.0% |
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 | 9 of 10 |
| Placebo | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sildenafil | Placebo |
|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 10 | 1 of 9 |
| Blurry vision | Eye disorders | 3 of 10 | 0 of 9 |
| Dizziness | General disorders | 1 of 10 | 1 of 9 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 10 | 0 of 9 |
| Headache | General disorders | 1 of 10 | 0 of 9 |
| Pleuritic pain | General disorders | 1 of 10 | 0 of 9 |
| Nasal Congestion | General disorders | 1 of 10 | 0 of 9 |
| Upper respirartory tract infection | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 9 |
| Epistaxis | General disorders | 1 of 10 | 0 of 9 |
| Rib Pain | Musculoskeletal and connective tissue disorders | 1 of 10 | 0 of 9 |
The posted serious adverse event figures are 0 affected participants among 10 at risk for sildenafil and 0 among 9 at risk for placebo. The serious adverse event term list is empty. These figures describe what is recorded for the study; they do not establish that no serious event could occur, particularly in a study with 10 enrolled participants.
The record also lists other adverse events for 9 of 10 participants at risk in the sildenafil group and 1 of 9 at risk in the placebo group. The terms or event descriptions for these other adverse events are not reported in the registry record. These counts should not be interpreted as a comparison of event rates or treatment-related risk without knowing how events were defined, collected, and attributed. The crossover design also means the treatment-period exposure and the way participants were counted for each treatment matter to interpretation.
Deaths are not reported in the registry record. The adverse event entries do not provide enough detail to assess timing, duration, severity beyond the serious-event classification, or relationship to treatment. In general, absence of a recorded serious event is not proof that an intervention is free from risk; it is a description of observed and posted events in this study.
12. What the Result Does, and Does Not, Mean
The primary outcome summaries report least-squares mean walking distances of 458.2 meters for sildenafil and 466.1 meters for placebo. The associated 95% confidence intervals are 380.0 to 536.0 meters and 388.0 to 544.0 meters, respectively. These figures describe the estimated distance under each treatment condition and the uncertainty around those estimates.
They do not report the estimated within-participant difference between sildenafil and placebo. They also do not give a confidence interval or p-value for that difference. In a crossover trial, the paired comparison is central: how much each participant's distance changes across treatment periods, and how those paired changes vary across participants, informs the treatment contrast. The treatment-specific means cannot reveal that pattern. The registry record does not report it.
The estimates therefore do not establish that either treatment produces a particular change in walking distance, nor do they establish equivalence or lack of a difference. A finding of no statistically significant difference would require a reported comparative analysis; the registry does not report one. Likewise, overlapping confidence intervals for treatment-specific means are not a formal test of the treatment contrast.
The record describes a small phase 2 study, with 10 participants enrolled. The posted outcome counts are 10 for sildenafil and 9 for placebo, and the reason for that difference is not reported in the registry record. The confidence intervals indicate meaningful uncertainty around each separate mean. The study record does not provide enough information to evaluate how precisely the treatment comparison itself was estimated.
The stated purpose included exercise capacity and lung function, but no secondary outcome analyses are reported. The primary result should not be extended to unreported lung-function outcomes, longer-term effects, or other patient groups. Overall, the posted data offer limited descriptive information about walking distances under the two conditions. They do not provide the comparative analysis needed to draw a statistical conclusion about the effect of sildenafil relative to placebo.
13. Why This Trial Matters Statistically
This study illustrates why design and analysis must be read together. A crossover trial has a different data structure from a parallel-group trial: participants can contribute measurements under more than one treatment, so the treatment comparison may depend on within-participant pairing. Reporting separate treatment means without a paired contrast leaves the main design-based comparison unclear.
The outcome is clinically interpretable as a distance walked during a standardized-duration task, and the registry reports its units and timeframe. At the same time, the primary outcome is a continuous measure whose estimate is accompanied by a confidence interval. The interval is essential to understanding precision; the point estimate alone would give an incomplete account. Here, the treatment-specific estimates have broad reported intervals, and the registry does not report an interval for the contrast.
The record also shows why registry completeness matters. It identifies the outcome, treatment sequences, enrollment, and adverse event counts, but does not report the model, missing-data approach, analysis population, or multiplicity strategy. Those omissions prevent readers from determining how closely the reported summaries reflect the crossover structure and the planned analysis.
The study is marked completed, yet its registry record lists no analyses and does not report secondary outcome results. That distinction between study completion and a complete public statistical account is important. The available figures should be interpreted as limited descriptive evidence, not as a substitute for a prespecified and fully reported comparative analysis.
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 primary limitation of the posted result is that it gives treatment-specific least-squares means and confidence intervals but no direct sildenafil-versus-placebo contrast. There is no reported comparative confidence interval, test statistic, or p-value. In a crossover design, separate summaries cannot show the within-participant changes that ordinarily inform the treatment comparison.
The registry does not report the statistical model, its covariates, the handling of treatment period or sequence, or whether possible carryover was assessed. Although the sequences include washout, the washout duration is not reported. The registry also does not describe the procedures used to measure walking distance or the detailed masking methods.
The primary outcome counts are 10 for sildenafil and 9 for placebo, while enrollment is 10. The reason for this difference, the missing-data status, and the intended analysis population are not reported in the registry record. Without these details, readers cannot assess whether the available outcome data represent all randomized participants or how incomplete paired measurements affected analysis.
The trial enrolled 10 participants, which limits the amount of information available in the posted estimates. The confidence intervals are broad, but the registry does not provide a comparative interval from which to assess the precision of the treatment contrast. The protocol's sample-size justification is not reported in the registry record.
Finally, the record lists secondary outcomes but does not report their analyses, and it does not describe a multiplicity strategy or analysis plan. These reporting gaps constrain interpretation of both the primary outcome and the broader exercise-capacity and lung-function questions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sildenafil for Chronic Obstructive Pulmonary Disease — NCT00104637.
- Registry record last updated 2012-05-21; status last verified 2012-05.
- Results first posted 2012-05-21.
- 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
NCT00104637 is a completed phase 2 randomized, triple-masked, placebo-controlled crossover study titled Sildenafil for Chronic Obstructive Pulmonary Disease. It enrolled 10 participants and listed sequences of sildenafil followed by washout and placebo, or placebo followed by washout and sildenafil.
The primary outcome was 6 Minute Walk Distance in meters, measured during Period 1 and Period 3, within 8 weeks. The registry reports least-squares means of 458.2 for sildenafil and 466.1 for placebo, with 95% confidence intervals of 380.0 to 536.0 and 388.0 to 544.0. The treatment contrast and analysis details are not reported in the registry record.
The record lists 11 outcome measures and 9 secondary outcomes but 0 analyses. Serious adverse events were recorded for 0 participants in each group; other adverse events were recorded for 9 of 10 at risk for sildenafil and 1 of 9 at risk for placebo. The other adverse event terms are not reported in the registry record.