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 Treatment for Mild TBI (NCT03598140), a randomized phase 2 study. The primary outcome is Arterial Spin Labeling.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03598140 |
| Phase | Phase 2 |
| Condition | Vascular System Injuries, Concussion, Brain, Post-Concussion Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Texas Southwestern Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The registry description refers to athletes and healthy controls in connection with cerebral blood flow measurement before and after treatment. It also frames the research goal around people who have experienced traumatic brain injury. The eligibility criteria, participant characteristics, and the relationship between these populations are not reported in the registry record.
Intervention
Sildenafil citrate at 60mg, delivered as either a single treatment or once a day for 14 days, depending on the assigned group. The registry lists sildenafil as a drug intervention.
Comparator
A placebo oral capsule, also assigned as either a single treatment or once a day for 14 days, depending on the assigned group.
Primary question
The primary outcome is arterial spin labeling, with cerebral blood flow measured before and after sildenafil treatment. The registry’s stated research goal is to test whether sildenafil normalizes cerebral blood flow and improves cognitive outcomes after traumatic brain injury. A results-based comparison between sildenafil and placebo is not reported in the registry record.
The question has two related but distinct aspects: whether cerebral blood flow changes after treatment and whether any such change differs between randomized treatment groups. A before-and-after measure within a group alone would not establish a treatment contrast; a randomized comparison would ordinarily assess the difference in outcomes between assigned groups. The registry record does not report an estimated contrast, its uncertainty, or a cognitive outcome result.
The listed secondary outcomes include the Rivermead Post Concussion Symptoms Questionnaire, the Hopkins Verbal Learning Task, and BOLD MRI with hypercapnia. They cover symptoms, verbal learning, and an imaging measure, but their role in any completed analysis is not reported. The record lists four outcome measures in total; the details and results for the remaining measure are not fully described in the available entry.
3. Trial Design
The registry identifies this as a phase 2, randomized, double-masked, parallel trial. Enrollment is listed as 22. The trial status is terminated. Its recorded start date is 2018-07-25, and its primary completion date is 2019-05-29. The reason for termination and the number of participants who actually entered or completed each treatment group are not reported in the registry record.
The interventions are sildenafil citrate and placebo oral capsule. The arm descriptions distinguish single treatment from repeated treatment once a day for 14 days. The registry does not explain how these treatment schedules map to the groups, whether they were separate study cohorts, or how participants were assigned between schedules. It also does not report the dosing schedule for placebo beyond the parallel descriptions of single or repeated treatment.
Random allocation is intended, in general, to balance measured and unmeasured characteristics between groups on average, while masking is intended to reduce influences of treatment knowledge on participants or study conduct. Those are general design principles, not evidence that masking was maintained or that balance was achieved in this trial. The registry record does not describe the allocation sequence, concealment procedures, who was masked, or whether masking was assessed.
The primary outcome is titled Arterial Spin Labeling and is described as measuring cerebral blood flow in athletes and healthy controls before and after sildenafil treatment. Its timeframe is recorded as 3 years. How that timeframe relates to the two treatment schedules, participant follow-up, or the specific outcome assessments is not explained. Eligibility criteria, study sites, participant flow, protocol deviations, and the statistical analysis plan are not reported in the registry record.
The registry states that the principal investigator left the institution and that efforts to locate the data were exhausted; consequently, no results are available to be reported. This explains the absence of results in the record but does not establish why the trial was terminated or what happened to individual participants.
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 | Placebo Oral Capsule | Sildenafil Citrate |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 9 | 11 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Placebo Oral Capsule | Sildenafil Citrate |
|---|---|---|
| enrolled but didn't start | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The PI has left the institution, all efforts to locate the data have been exhausted and therefore no results are available to be reported
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: The PI has left the institution, all efforts to locate the data have been exhausted and therefore no results are available to be reported
| Characteristic | Unit | Placebo Oral Capsule | Sildenafil Citrate | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Age, Categorical: <=18 years | — | — | — | |
| Age, Categorical: Between 18 and 65 years | — | — | — | |
| Age, Categorical: >=65 years | — | — | — | |
| Sex: Female, Male: Female | — | — | — | |
| Sex: Female, Male: Male | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Arterial Spin Labeling, measured over 3 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled Arterial Spin Labeling. Its description says cerebral blood flow will be measured in athletes and healthy controls before and after sildenafil treatment. The registry’s stated research goal is to test whether sildenafil can normalize cerebral blood flow after traumatic brain injury, making cerebral blood flow a direct measure of the proposed vascular outcome.
In general, arterial spin labeling is an MRI approach used to estimate cerebral blood flow without relying on an injected contrast agent. Cerebral blood flow is relevant to the trial’s stated question because the record describes traumatic cerebral vascular injury as involving changes in blood flow and identifies normalization of cerebral blood flow as a treatment goal. This is a general explanation of the measurement’s role, not a reported finding from the trial.
The record does not give the endpoint’s unit, summary parameter, dispersion measure, or the exact assessment schedule. Although the timeframe is stated as 3 years, the meaning of that timeframe for this endpoint is not clarified. The record also does not report baseline or follow-up values, a between-group comparison, or an estimate of change. Thus, the endpoint’s planned purpose can be described, but its observed magnitude and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
No primary outcome results are available to interpret. The record explicitly says that the principal investigator left the institution, efforts to locate the data were exhausted, and no results are available to be reported. It therefore gives no cerebral blood flow values before or after treatment, no comparison between sildenafil and placebo, and no estimate of uncertainty around a treatment contrast. This is an absence of reported results, not evidence that the groups had the same outcome or that no change occurred.
The trial status is terminated, and enrollment is listed as 22. Neither fact reveals how many participants contributed outcome data, whether the planned treatment schedules were completed, or whether the analysis followed randomized assignment. Those details are not reported in the registry record. The reason for termination is also not reported, so the status alone should not be used to infer a safety issue, lack of efficacy, or a particular operational problem.
The record lists secondary outcomes involving post-concussion symptoms, verbal learning, and BOLD MRI with hypercapnia, but it does not provide their results. It reports four outcome measures in total, while the primary outcome is not reduced to one comparison across its categories or time points. Without outcome values and a defined comparison, statistical significance, direction of effect, and clinical importance cannot be evaluated.
The adverse-event record lists zero for the counts of participants at risk and affected in both the serious and other event categories, as well as zero deaths in each group. These entries do not establish that no adverse events occurred: the record does not explain whether event information was collected, whether the zero values indicate no events or no submitted data, or how many participants were included in safety follow-up. The absence of reported outcome data makes it especially important not to treat these entries as comprehensive evidence about safety.
The planning assumptions describe hypothetical sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. No observed effect estimate is reported in this record, and no numerical planning results are available in the registry record described for this analysis. Such planning values, when available, would be design illustrations rather than observed power or evidence that a trial has established an effect.
Overall, the registry supports a description of the design and intended measurements, but not an estimate of treatment effect. Precision cannot be characterized without results and uncertainty measures such as confidence intervals. The central statistical conclusion is therefore limited: the registry record contains no analyzable primary outcome result.
9. Statistical Methods Explained
Several statistical ideas help clarify what can and cannot be learned from this record. The explanations below are general; the registry does not report that a particular analysis was carried out.
What would a randomized comparison estimate?
In general, a randomized trial estimates a contrast between outcomes in groups assigned to different interventions. For a continuous measure such as cerebral blood flow, an analysis might compare group averages at follow-up, compare changes from baseline, or use a model that accounts for baseline measurements. These approaches answer related but not identical questions and can differ in precision. The registry record does not specify which approach was planned or used, and no outcome estimates are reported.
A before-and-after change within the sildenafil group would not, by itself, separate a treatment effect from changes that might also occur over time in the placebo group. The randomized comparison is important because it uses the placebo group as a reference for changes unrelated to the active intervention. This is a general principle; the record does not provide the data needed to make that comparison for this trial.
What does a confidence interval communicate?
In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure and its assumptions. Its width conveys precision: a narrower interval indicates greater precision than a wider interval, all else equal. An interval that includes a value representing no difference would indicate that the data do not clearly distinguish that value from the estimated contrast at the interval’s confidence level. No estimate or confidence interval is reported for the primary outcome here, so neither direction nor precision can be assessed.
A p-value, if reported, would describe how surprising data at least as extreme as those observed would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The registry record reports no p-value or primary outcome analysis. Statistical significance therefore cannot be judged, and it would not substitute for an estimate and its uncertainty even if a p-value were available.
How should the planning assumptions be understood?
The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe an illustration based on a fraction of an observed effect. In general, sample-size planning asks how many participants would be needed under stated assumptions to detect a target effect with a chosen probability of rejecting a null hypothesis when that effect is present. The assumptions are not a description of what was observed in this trial, and planning quantities are not observed power.
An effect-based illustration depends on the effect used as its starting point and on assumptions about variability, allocation, and the analysis. If the starting effect is uncertain or comes from a small study, the resulting planning estimates can also be uncertain. No primary effect estimate or outcome variability is reported in the registry record, and no numerical planning illustrations are stated in the record details available for this analysis. The registry also does not report its own sample-size justification. It would therefore be inappropriate to treat an illustrative planning calculation as the trial’s original design rationale.
Why can outcome structure matter?
A single outcome can be recorded at more than one time point, across multiple categories, or in more than one population. Each possible comparison may answer a different question. The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. The exact structure and intended primary contrast are not reported. Without that definition, it is not possible to identify a single effect estimate or determine which comparison should anchor interpretation.
In general, making many statistical comparisons increases the chance of obtaining at least one apparently unusual result by chance. Multiplicity methods can control or describe that risk, but their choice depends on which outcomes and comparisons were prespecified and which are considered confirmatory. The registry record does not report a multiplicity strategy. This absence does not prove that none was planned; it means the record does not document one.
What can the record say about model assumptions?
Statistical models rely on assumptions suited to the outcome and design. For continuous outcomes, assumptions may concern the distribution of residuals, the relationship between group and outcome, and whether observations are independent. Repeated measurements may call for methods that account for within-participant correlation. The primary endpoint description includes measurements before and after treatment, but the registry does not identify an analysis model or explain how repeated measurements would be handled.
Over-dispersion is a general concern for some count outcomes: observed variability can exceed what a simple model assumes. A model that fails to account for excess variation may report uncertainty that is too small. This is a general statistical concept, not a claim that over-dispersion applies to the trial’s cerebral blood flow outcome. The registry does not report a count-outcome analysis or model diagnostics.
Finally, an analysis population matters. An intention-to-treat analysis generally compares participants according to randomized assignment, while a per-protocol analysis restricts attention according to treatment or follow-up criteria. These answer different questions and can be affected differently by missing outcomes or deviations. The registry record does not state which population was analyzed. Since no results are available, no model-based estimate, diagnostic assessment, or sensitivity analysis can be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary outcome and secondary outcomes, but it does not report a complete analysis plan. The named secondary outcomes are the Rivermead Post Concussion Symptoms Questionnaire, the Hopkins Verbal Learning Task, and BOLD MRI with hypercapnia. Four outcome measures are listed in total. The primary outcome is noted as having several categories or time points and is not reduced to one comparison, leaving the intended primary contrast unclear.
In general, multiplicity arises when researchers examine multiple outcomes, time points, groups, or statistical contrasts. The more comparisons considered, the greater the opportunity for chance findings. Prespecifying a primary contrast and defining how secondary analyses will be interpreted can help readers distinguish confirmatory questions from exploratory ones. The registry record does not report whether a multiplicity adjustment, hierarchy of outcomes, or other strategy was planned. It also does not report interim analyses or stopping rules; their presence or absence cannot be inferred from this omission.
Missing outcome data are central because the registry says no results are available after efforts to locate the data were exhausted. It does not report how many participants had missing measurements, why data might be missing, or whether any missing-data method was planned. In general, missing-data methods rely on assumptions about why observations are unavailable. Without participant flow and outcome availability, those assumptions cannot be assessed.
The analysis population is not reported in the registry record. There is no account of whether analyses were to follow randomized assignment, include only participants who completed treatment, or use another definition. No sensitivity analyses are described. These omissions prevent assessment of how exclusions, treatment adherence, or unavailable measurements might have affected any estimate. They do not establish that a particular analysis or sensitivity method was not performed; they indicate that it is not documented in the record.
11. What the Result Does, and Does Not, Mean
The record describes a randomized phase 2 trial comparing sildenafil with placebo and identifies cerebral blood flow measured by arterial spin labeling as the primary outcome. It also states an intention to examine cognitive outcomes and lists secondary measures related to post-concussion symptoms, verbal learning, and MRI with hypercapnia. These registry entries describe the study’s questions and design; they are not findings about treatment effects.
No primary or secondary outcome results are available to be reported. Consequently, the record cannot establish whether cerebral blood flow changed, whether any change differed between treatment groups, or how precisely a treatment contrast was estimated. It also cannot show whether the listed cognitive or symptom measures changed. Absence of results does not mean that the intervention had no effect; it means an effect cannot be determined from the registry record.
The terminated status does not, on its own, explain the outcome of the trial. The registry identifies the principal investigator’s departure and unsuccessful efforts to locate data as the reason no results are reported, but it does not state why the trial was terminated. The enrollment figure is not a participant-flow account and does not establish how many people contributed data to a particular outcome.
Similarly, the zero entries in the adverse-event record should not be treated as proof that the treatments caused no adverse events. The record does not explain the event-count reporting or give the number of participants with safety follow-up. A statistical interpretation must distinguish an absent result from a result close to no difference, and distinguish zero recorded counts from evidence of complete ascertainment. Neither distinction can be resolved using the information in the record.
In general, a trial result should be interpreted using the estimated effect, its uncertainty, the outcome definition, and the analysis population. Here, the design and intended measures can be described, but those result components are unavailable. No conclusion about benefit, lack of benefit, or safety follows from the registry entry alone.
12. Why This Trial Matters Statistically
This trial illustrates a key distinction in clinical-trial interpretation: a clearly stated research question is not the same as an available result. The record describes randomization, masking, treatment groups, and a primary measure aligned with a stated interest in cerebral blood flow. Yet it reports no outcome data, so there is no estimate to quantify or uncertainty interval to assess.
For biostatisticians and clinical researchers, this makes reporting completeness part of the evidence itself. A status, enrollment figure, and endpoint description cannot replace participant flow, outcome summaries, analysis methods, and treatment contrasts. Without those elements, readers cannot judge the direction or precision of an effect, check how the reported outcome relates to the planned question, or assess whether missing measurements could influence conclusions.
The record also highlights why primary outcomes need an explicit comparison when measurements involve multiple categories or time points. A clear definition of the target contrast supports consistent analysis and interpretation. If several outcomes or comparisons are considered, a documented multiplicity strategy helps clarify how confirmatory claims should be evaluated. Those details are not reported in the registry record.
Finally, planning illustrations and trial results answer different questions. Planning depends on assumptions about the effect to detect and the analysis, while an observed result depends on data actually collected. The planning assumptions stated for this trial do not supply evidence of an observed effect, and no result-based precision assessment is possible. The statistical value of the registry entry is therefore primarily descriptive: it identifies the intended design and outcome, while also making clear that the result needed for inference is unavailable.
13. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is the absence of reported outcome data. The registry explicitly states that the principal investigator left the institution, efforts to locate the data were exhausted, and no results are available to be reported. Consequently, no treatment-effect estimate, uncertainty measure, or outcome-level interpretation can be made.
The record gives enrollment as 22 but does not provide participant flow, numbers assigned to each group, numbers completing treatment, or numbers with primary outcome measurements. It does not report baseline characteristics or describe exclusions. The enrollment figure therefore cannot be treated as the analyzed sample size or as evidence that all enrolled participants contributed to the endpoint.
The primary endpoint description leaves important details unspecified. The measure is titled Arterial Spin Labeling and is described as cerebral blood flow measured before and after treatment in athletes and healthy controls, with a timeframe of 3 years. The exact time points, units, summary measure, and connection between that timeframe and the treatment schedules are not reported. The record also does not clarify how athletes, healthy controls, and people with traumatic brain injury relate to the enrolled trial population.
The intervention descriptions include single treatment and daily treatment for 14 days, but the record does not explain the allocation of participants across those schedules or identify the specific primary comparison. It also does not report adherence, protocol deviations, masking details, or the statistical analysis plan. The status is terminated, but the reason for termination is not reported.
Finally, secondary-outcome results, missing-data handling, the analysis population, multiplicity procedures, and safety-event ascertainment are not reported. These limitations restrict both efficacy and safety interpretation. They should be understood as gaps in the registry record, not as proof that the omitted information was never collected or that a particular analysis was not performed.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Sildenafil Treatment for Mild TBI — NCT03598140.
- Registry record last updated 2020-11-19; status last verified 2020-10.
- Results first posted 2020-11-19.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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17. Record Summary
The registry identifies NCT03598140, titled “Sildenafil Treatment for Mild TBI,” as a phase 2 randomized, double-masked, parallel trial sponsored by the University of Texas Southwestern Medical Center. Enrollment is listed as 22, and the status is terminated. The recorded start date is 2018-07-25 and the primary completion date is 2019-05-29.
The trial lists sildenafil citrate and placebo oral capsule, with descriptions of single treatment or daily treatment for 14 days. The primary outcome is arterial spin labeling, described as measuring cerebral blood flow before and after sildenafil treatment. Listed secondary outcomes concern post-concussion symptoms, verbal learning, and BOLD MRI with hypercapnia.
The registry states that the principal investigator left the institution, efforts to locate the data were exhausted, and no results are available to be reported. It does not report a primary outcome estimate, analysis method, or reason for termination. The record therefore supports a summary of the intended study, but not a statistical conclusion about its outcomes.