Use of Sildenafil (Viagra) to Alter Fatigue, Functional Status and Impaired Cerebral Blood Flow in Patients With CFS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Sildenafil (Viagra) to Alter Fatigue, Functional Status and Impaired Cerebral Blood Flow in Patients With CFS (NCT00598585), a randomized phase 4 study. The primary outcome is Change in Fatigue Impact Scale at 6 Weeks.

2. Clinical Question

The study addresses whether the groups had different observed changes in a self-reported measure of fatigue impact. On the scale described in the registry, higher scores indicate more severe fatigue impact. The posted means are changes from baseline, so negative values indicate that scores decreased over the measured interval. This direction can be understood from the scale definition, but the conflicting time references limit clarity about precisely when the change was measured.

The registry lists 12 participants as enrolled. The outcome results list 5 participants in the sildenafil group and 6 in the placebo group. The record does not explain the difference between the enrollment figure and the group sizes reported for this outcome. It also does not report detailed eligibility criteria, participant characteristics, or the analysis population. Those omissions limit assessment of who the posted estimates represent and how broadly they might apply.

3. Trial Design

This is a Phase 4, randomized, double-masked, parallel-group study sponsored by Charles Drew University of Medicine and Science. The interventions listed are Sildenafil (Viagra) and placebo. The registry lists Chronic Fatigue Syndrome as the condition and reports enrollment of 12. The status is completed. The study start is recorded as 2002-07, and primary completion as 2010-12; these entries do not by themselves establish the duration of an individual participant’s treatment or follow-up.

The parallel-group design means participants were assigned to one of the two intervention groups rather than being described as crossing between treatments. Random allocation can support a fair comparison by reducing systematic differences between groups at assignment, while masking is intended to limit influences from knowing the assigned intervention. The registry does not report the randomization procedure, allocation concealment, masking procedures, or whether masking was checked. Those details are not reported in the registry record.

The primary outcome is titled Change in Fatigue Impact Scale at 6 Weeks. Its description, however, states that scores are calculated at baseline and 6 months and compared with baseline. The registry record does not clarify whether the intended assessment was at 6 weeks or 6 months. This unresolved inconsistency matters when interpreting the reported change and the timing of the primary comparison.

The reported outcome groups contain 5 participants assigned to sildenafil and 6 assigned to placebo. The record does not explain how these group sizes relate to the enrollment figure of 12, whether any participants were excluded from the outcome analysis, or whether the posted group sizes reflect all randomized participants. The protocol, adherence information, and details of treatment duration are not reported in the registry record. The trial’s design can therefore be described from its registration labels, but several operational details needed to assess implementation are unavailable.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Fatigue Impact Scale at 6 Weeks, measured over 6 weeks.

The primary endpoint is change in Fatigue Impact Scale score. The registry describes a questionnaire with 42 questions, each answered from 0, meaning no problem, to 4, meaning extreme problem. It reports a minimum score of 0 and a maximum score of 148, with higher scores indicating more severe fatigue impact. The outcome is a continuous measure, and the posted arm summaries are means with standard deviations.

A change score compares a participant’s follow-up score with that participant’s baseline score. A negative change therefore represents a decrease in the scale score; given the stated direction of the scale, lower scores indicate less severe fatigue impact. Group averages describe the average change among the participants represented in each arm. They do not show how much individual participants varied, which is why the standard deviations are also relevant.

A fatigue-impact questionnaire is used to quantify how fatigue affects reported functioning and daily experience, rather than relying only on a general statement that fatigue is present. Such a scale can make change easier to summarize consistently across participants. This is a general explanation of the role of a continuous patient-reported measure; the registry does not report why this particular instrument was selected or whether it was validated for this study population.

The endpoint timing is unclear: its title says 6 weeks, while its description refers to baseline and 6 months. The registry record does not clarify which assessment interval generated the posted means. That ambiguity prevents a confident interpretation of the time period represented by the outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported test address?

The registry identifies a two-sided t-test comparing the sildenafil and placebo groups. In general, a t-test evaluates whether the data are compatible with a null hypothesis of no difference in group means, using the observed variability and sample sizes. A two-sided test allows evidence in either direction to count against that null. The registry reports p < 0.05, but does not give the exact p-value, test statistic, degrees of freedom, or a confidence interval.

A p-value is conditional on the null model and the test’s assumptions. It describes how unusual data at least as incompatible with the null would be if the null and assumptions held. It does not measure the probability that an observed result happened “by chance,” establish that a treatment effect is important, or show how likely a result is to recur. These are general interpretations of p-values, not additional findings from this trial.

Why do the means need uncertainty measures?

The posted means are summaries of observed change scores. The standard deviation describes the spread of participant scores around a group mean. It is not itself an estimate of the precision of the difference between group means. Precision depends on the spread and the amount of information in the groups, as well as the method used to estimate the contrast.

A confidence interval is a general way to express uncertainty about an estimated effect. It gives a range of values compatible with the data under the specified statistical procedure. Its width conveys precision: wider intervals indicate less precision. No confidence interval for the two-group comparison is reported in the registry record. The sponsor-reported p-value cannot substitute for that missing range, because a thresholded p-value does not show the possible size of the contrast.

What does recalculation mean in this context?

A recalculation from posted summary statistics would be an unadjusted calculation based on the group means, standard deviations, and group sizes. It would not necessarily reproduce a sponsor analysis that used additional information or different assumptions. For this continuous two-arm outcome, values are missing or not estimable for a recalculated comparison. Consequently, no recalculated contrast or confidence interval is available to compare with the sponsor’s test. The registry does not flag a discrepancy between a recalculation and the sponsor analysis.

Even when a calculation can be reconstructed from summaries, it should be distinguished from the original trial analysis. A reconstructed estimate is useful as a check on what the summaries imply, but it cannot reveal choices that are not reported, such as adjustments or handling of missing observations. In this study, those details are not reported in the registry record, and a numerical reconstruction is not available.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model assumes. If a method underestimates variability, it can make uncertainty appear smaller than it is. This concept is especially relevant when a statistical model uses a specified variance structure. The posted analysis is described as a t-test, and the registry does not report an over-dispersion assessment or a variance adjustment. There is therefore no basis in the record to claim that over-dispersion was assessed or affected the result.

The standard deviations reported for the groups indicate that individual changes vary, but they do not alone establish a violation of the t-test assumptions. Assessment would require more information about the observed data and analysis procedure than the registry provides. This is a general methodological point, not a finding that the assumptions were or were not met.

How should planning illustrations be read?

The planning method described in the record uses a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantities are participants per arm. Such calculations are illustrations of sample sizes under stated assumptions; they are not evidence about the trial’s actual design rationale and are never observed power.

Using an observed effect as a planning reference can be uncertain, particularly when the observed group sizes are small. If an estimated effect is unstable, a planning calculation based on it will also be sensitive to that estimate. The registry does not report the trial’s own sample-size justification or the assumptions used when enrollment was planned. No conclusion about the original design target should be drawn from a planning illustration.

Power is a prospective design property under a set of assumptions, not a retrospective measure of whether a particular finding is true. A sample-size illustration cannot show that the study had a given probability of detecting an effect after observing its results. The record’s stated planning approach should therefore be read as a hypothetical design aid, distinct from the completed trial’s reported test.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Sildenafil", "Placebo")
n   <- c(5, 6)
m   <- c(-32.6, -1.5)
sp  <- c(31.5, 12.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Sildenafil  5  -32.600  31.500  -71.712  6.512
CARM  Placebo  6  -1.500  12.200  -14.303  11.303

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s analysis as a two-sided t-test comparing the sildenafil and placebo groups, with p < 0.05. It does not report a numerical test statistic, exact p-value, estimated between-group contrast, or confidence interval. The analysis is labeled as a superiority analysis.

A recalculated comparison from the posted continuous-outcome summaries is not available: the record indicates that values are missing or not estimable for a two-arm comparison. There is therefore no recalculated estimate or interval to set alongside the sponsor’s result. The registry does not flag a discrepancy between the sponsor analysis and a recalculation.

The sponsor’s test is the only reported inferential comparison in the record, but its thresholded p-value is not a full account of the result. It does not provide the magnitude or precision of the contrast, and it does not resolve the uncertainty over whether the outcome interval was 6 weeks or 6 months. The record also does not report whether the analysis adjusted for other variables or how missing observations were handled. Those features cannot be inferred from the test label.

Accordingly, the posted analysis can be described as reporting a statistically significant result under the sponsor’s stated test threshold, while the size and precision of the comparison remain unavailable. The group means and standard deviations provide descriptive information, but they do not fill those gaps.

12. Multiplicity, Missing Data and Analysis Populations

The registry reports 1 primary outcome measure and 0 posted secondary outcomes, along with 1 reported analysis. These entries describe what is posted; they do not establish that the study measured no other outcomes or that no other analyses were conducted. The protocol’s full outcome plan and any prespecified analysis hierarchy are not reported in the registry record.

Multiplicity arises when multiple outcomes, time points, comparisons, or analyses create multiple opportunities to observe a result that crosses a chosen significance threshold. In general, prespecifying a primary analysis and accounting for related tests can help readers understand how a reported p-value fits within the larger analysis plan. The record does not report whether any multiplicity adjustment was planned or applied. The mismatch between the 6 weeks in the outcome title and 6 months in the description makes the intended primary time point particularly unclear.

Missing-data handling is also not reported in the registry record. The record gives group sizes for the posted endpoint, but does not state whether all randomized participants contributed an outcome, how missing scores were treated, or whether any imputation was used. The listed enrollment is 12, while the outcome groups list 5 and 6 participants; the record does not explain this difference. It would be inappropriate to assume that participants without posted outcomes had a particular reason for being absent or that their data were handled in a specific way.

The analysis population is not reported in the registry record. It is therefore unclear whether the analysis followed all randomized participants as assigned, included only participants with observed outcomes, or used another population definition. The randomization label alone does not answer that question.

Interim analyses, stopping rules, protocol deviations, and the statistical analysis plan are not reported in the registry record. Their absence from the record should not be taken as evidence that such procedures were or were not used. These reporting gaps limit assessment of how the single posted p-value relates to the study’s planned analyses.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event results list 0 serious events among 5 participants at risk in the sildenafil group and 0 among 6 participants at risk in the placebo group. These are the serious-event counts recorded for the groups. They do not establish that no serious events could occur, and the small numbers at risk provide limited information about uncommon events.

The registry also reports 1 other, non-serious adverse event in the sildenafil group among 5 participants at risk, and 0 in the placebo group among 6 participants at risk. The record does not provide the term or nature of that event. It does not report further details about event timing, severity beyond the category, relationship to the intervention, or whether participants experienced more than one event.

Deaths are listed as null for both groups. That means death counts are not reported in the registry record; it should not be interpreted as a reported count of zero. No top serious adverse-event terms are listed, consistent with the posted serious-event counts of zero, but the record offers little detail for broader safety assessment. These figures describe the recorded adverse-event information and are not a basis for medical advice or a comprehensive comparison of safety.

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

The posted data describe mean changes in Fatigue Impact Scale scores for the sildenafil and placebo groups, with their group sizes and standard deviations. The registry also reports a two-sided t-test result of p < 0.05. This is evidence that the sponsor’s analysis found a result inconsistent with its null hypothesis at the reported threshold, under that test’s assumptions. It does not by itself establish the size, precision, or practical importance of the group contrast.

The scale direction gives context for the signs of the mean changes: higher scores indicate more severe fatigue impact, so a negative change represents a decrease in score. The record does not resolve whether these changes refer to 6 weeks or 6 months. That ambiguity prevents a clear account of the time interval represented by the primary result.

The results do not show how individual participants changed, whether the group means are sensitive to particular observations, or how missing outcomes were handled. There is no reported confidence interval for the contrast, and no recalculated comparison is available. Without those details, the uncertainty around the magnitude cannot be described fully.

Randomization and masking are important design features, but the record does not provide enough information to assess how they were implemented or how the analysis population was defined. Nor does the posted result alone establish that the same pattern would occur in another population or setting. Generalization depends on participant characteristics, study conduct, and the relevance of the measured outcome and time point; these are incompletely documented.

The result should therefore be read as a small study’s posted descriptive summaries accompanied by a sponsor-reported statistical test. It does not establish that sildenafil works or does not work, and it does not support medical decisions. The record leaves substantive uncertainty about timing, precision, missing data, and analysis populations.

15. Why This Trial Matters Statistically

This trial illustrates why a reported p-value is only one component of statistical interpretation. The registry gives group means, standard deviations, and a sponsor-reported test threshold, but not an estimated contrast with a confidence interval. Readers can see the direction and spread of the observed changes, yet cannot assess the precision or plausible magnitude of the between-group result from the posted inferential information alone.

The record also highlights how endpoint definitions affect statistical meaning. A change score depends on a clearly specified baseline and follow-up assessment. Here, the outcome title states 6 weeks while the description refers to baseline and 6 months. Statistical summaries cannot resolve a discrepancy in the definition of the measurement interval; transparent reporting of the endpoint and timing is essential to interpret what the estimate represents.

The enrollment and outcome group sizes provide another useful reporting lesson. The registry lists enrollment of 12, while outcome results list 5 and 6 participants in the respective groups. The record does not explain the difference or identify the analysis population. Readers therefore cannot determine from the posted information whether all randomized participants contributed to the endpoint analysis or how any missing observations were handled.

Finally, the planning approach described in the record is distinct from the study’s original design justification and from retrospective power. Planning illustrations based on an observed effect can be sensitive to the estimate, especially with small group sizes. They should not be treated as proof that the trial was adequately powered or as a measure of the credibility of its observed result. These distinctions are central to sound interpretation of clinical trial statistics.

16. 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.

Several limitations specific to this record constrain interpretation. The primary outcome title identifies assessment at 6 weeks, whereas its description refers to measurements at baseline and 6 months. The record does not explain which timing applies to the posted results. Because the amount of change depends on the measurement interval, this ambiguity affects the meaning of the primary endpoint.

The registry reports enrollment of 12 and outcome group sizes of 5 and 6, without explaining how these figures relate. No analysis population is identified, and missing-data methods are not reported. It is therefore unclear whether the outcome summaries represent all randomized participants, only those with observed measurements, or another defined group.

The reported inferential information is limited to a two-sided t-test and p < 0.05. The registry does not provide an estimated between-group contrast, confidence interval, exact p-value, or test statistic. A recalculated comparison is not available for this continuous outcome. Consequently, the precision and magnitude of the primary comparison cannot be assessed from the posted analysis details.

Further trial details are not reported in the registry record, including eligibility criteria, participant characteristics, treatment administration details, randomization procedures, masking procedures, protocol deviations, and the statistical analysis plan. The record does not describe whether other outcomes or interim analyses were planned. These are reporting limitations; they do not establish that the procedures were absent or that any particular bias occurred.

The posted adverse-event information is also sparse. Serious-event counts are reported as zero in both groups, while deaths are not reported. The nature of the other adverse event is not given. The small group sizes and limited event descriptions restrict what can be concluded from the safety entries.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Use of Sildenafil (Viagra) to Alter Fatigue, Functional Status and Impaired Cerebral Blood Flow in Patients With CFS — NCT00598585.
• Registry record last updated 2017-06-27; status last verified 2017-04.
• Results first posted 2017-06-27.
• 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.

20. Record Summary

The registry identifies NCT00598585 as a completed Phase 4 randomized, double-masked, parallel-group study sponsored by Charles Drew University of Medicine and Science. The interventions are sildenafil and placebo, and enrollment is listed as 12. The primary outcome is change in Fatigue Impact Scale score, described as a continuous measure in which higher scores indicate more severe fatigue impact.

The posted outcome results list mean changes of -32.6 for sildenafil and -1.5 for placebo, with standard deviations of 31.5 and 12.2 and group sizes of 5 and 6. The sponsor-reported analysis is a two-sided t-test with p < 0.05. A recalculated comparison is not available, and no confidence interval for the contrast is reported.

The record does not resolve whether the primary assessment was at 6 weeks or 6 months, or explain the difference between enrollment and outcome group sizes. Missing-data methods, the analysis population, and further details of trial conduct are not reported in the registry record.