Evaluation of Contrast-Enhanced Ultrasound to Detect Endoleaks After Endovascular Aortic Aneurysm Repair: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Contrast-Enhanced Ultrasound to Detect Endoleaks After Endovascular Aortic Aneurysm Repair (NCT01005212), a registered phase not stated study. The primary outcome is Endoleak Detection.

2. Clinical Question

3. Trial Design

The registry describes this investigation as a cross-sectional survey of interobserver variability associated with CEUS for endoleak detection. Its brief summary states that CTA is used as the practice standard. Participants are described as undergoing imaging at the first follow-up visit after EVAR, including abdominal ultrasound examinations with and without contrast and CTA. The primary outcome timeframe is listed as “Same day outcome.” The study is marked COMPLETED, with a start date of 2008-01 and a primary completion date of 2010-09.

The registry lists enrollment as 20, while the brief summary says investigators will enroll 40 consecutive patients. The record does not explain whether these values refer to different enrollment stages, a change in plans, or an inconsistency. It is therefore not possible to determine the final enrolled sample from these statements alone. The record does not report participant flow, withdrawals, exclusions, or the number included in any analysis.

This is not presented as a randomized comparison. The record does not report allocation to treatment arms, and the safety listing is labeled “CEUS-Single Arm.” The brief summary describes paired imaging assessments rather than a treatment-versus-control design. The registry record does not report whether image readers were blinded to other imaging findings, whether readers assessed images independently, or how disagreements were resolved.

The listed sponsor is E. Peden, MD. The registry identifies one primary outcome measure and reports no statistical analyses. It does not report a protocol-level statistical plan, a sample-size justification, or details of interim analyses. The registry’s completion status indicates that the study is marked completed, but completion does not by itself establish that every planned analysis or result is available in the record.

4. Participant Flow and Accounting

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

Overall Study

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 Endoleak Detection, measured over Same day outcome.

The primary endpoint is “Endoleak Detection,” measured as a count of participants. The definition is persistent pulsatile intrasac color flow outside the stent-graft, and the stated timeframe is “Same day outcome.” This is a binary participant-level outcome: a participant either meets the stated detection definition or does not. The registry record does not report the observed count or a corresponding estimate.

In general, a defined endpoint makes clear what observation is being counted and at what time. A participant-level detection outcome is relevant to the stated aim because the study concerns identifying endoleaks after EVAR. However, the definition alone does not establish how consistently different observers applied it, how it was compared with CTA, or how accurate CEUS was. Those questions require results from the relevant assessments.

The brief summary also names interobserver variability, sensitivity and specificity compared with CTA, and the number and types of endoleaks detected as other endpoints. The registry record does not provide their results or operational definitions. It also does not state whether the primary count was intended to summarize CEUS findings, CTA findings, or a specific reader’s assessment. That lack of detail limits interpretation of the endpoint entry: its label and definition are available, but the relationship between the recorded primary outcome and the broader diagnostic objectives is not fully described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a cross-sectional imaging evaluation, not a randomized treatment comparison. The brief summary says participants would undergo ultrasound with and without contrast and CTA at the first follow-up visit after EVAR. A cross-sectional assessment examines measurements collected at a stated assessment period rather than following participants to compare longer-term outcomes. The listed primary timeframe is “Same day outcome.” This design description identifies the setting for the diagnostic question; it does not, by itself, establish how images were read or how the comparisons were analyzed.

What does interobserver variability mean?

In general, interobserver variability describes differences in the classifications or measurements made by different readers assessing the same material. For an imaging study, it can indicate whether readers reach similar conclusions when deciding whether an endoleak is present or describing its characteristics. Agreement can be reported as a simple proportion of matching assessments or with a statistic that adjusts for agreement expected by chance. Those approaches answer related but not identical questions. The registry record does not report which approach was planned or used, how many readers participated, or the resulting agreement.

How should CTA comparison be understood?

The brief summary identifies CTA as the practice standard for evaluating CEUS. In general, a reference method provides the basis for classifying findings when estimating diagnostic accuracy. Sensitivity describes the proportion of reference-positive cases also identified by the method under evaluation; specificity describes the proportion of reference-negative cases also classified as negative. These definitions are general explanations, not numerical results from this study. To estimate either quantity, the paired classification results must be available. The registry record does not report those results, the accuracy estimates, or their uncertainty.

Agreement with a reference method and agreement between readers are distinct properties. Readers could agree with each other while differing from the reference method, or could vary in their assessments even if the overall results appeared similar. A diagnostic accuracy analysis and an interobserver agreement analysis therefore address separate aspects of the study question. The record names both aims but does not provide the methods or results needed to assess either one.

What does the endpoint count represent?

The primary measure is a count of participants meeting the stated endoleak definition. In general, a binary participant outcome records whether the qualifying event or finding is present for each participant. A count is interpretable only when the population included in the analysis and the rule for determining the outcome are clear. The registry gives the definition as persistent pulsatile intrasac color flow outside the stent-graft, but does not report an observed count, the analysis population, or the handling of uncertain and missing assessments.

The summary also lists sensitivity, specificity, interobserver variability, and characterization of the number and types of endoleaks as other endpoints. These outcomes require different summaries and may rely on different units of analysis. For example, diagnostic accuracy compares paired test classifications, whereas a count of participants describes how many people meet an endpoint definition. The registry record does not explain how these measures were related, whether any endpoint was prioritized beyond the listed primary measure, or how multiple reader assessments were incorporated.

What can planning assumptions tell readers?

General sample-size calculations estimate the amount of information that may be needed under specified assumptions; they are not observed results and do not establish the study’s actual design. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those are planning assumptions, not evidence that the trial used two arms or equal allocation. The registry does not describe a randomized comparison, and it does not report the trial’s own sample-size justification. Any sample-size planning illustration should therefore be read as a separate calculation, not as a description of enrollment or observed power.

In general, over-dispersion occurs when variability in the data exceeds what a statistical model assumes. When present, it can make standard errors too small if the analysis does not account for the extra variability. The registry does not report a statistical model or any analysis of over-dispersion, and no conclusion about its presence or relevance can be drawn for this study.

More broadly, a confidence interval expresses the uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, but it does not remove possible bias in the measurement or design. The registry record reports no confidence intervals or estimates to interpret. It also does not report an analysis plan, covariate adjustment, missing-data method, or interim-analysis procedure. These methods cannot be inferred from the study’s stated aims.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Single Arm")
n      <- c(20)
events <- c(9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Single Arm  20  9  45.0  23.1  68.5  25.8  65.8  25.7  66.0

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome measure and describes several additional objectives: interobserver variability, sensitivity and specificity compared with CTA, and the number and types of endoleaks detected. It does not report a statistical analysis plan explaining how these objectives were prioritized or how multiple analyses were handled. The registry also reports no analyses. It is therefore not possible to determine whether any multiplicity adjustment was planned or used, or whether the additional objectives were exploratory.

In general, multiplicity arises when several hypotheses or outcomes are examined. Testing multiple questions can increase the chance of a chance-positive finding if each is interpreted without regard to the number of analyses. How to address that issue depends on the intended claims and analysis plan. No such plan is reported in the registry record, so the implications cannot be assessed for this study.

The registry does not report missing outcome data, exclusions, withdrawals, or the number of participants with assessable images. It also does not describe how indeterminate imaging results or disagreement between readers were handled. Missingness can matter when the availability of an assessment is related to the outcome or to participant characteristics. In general, analyses based only on observed assessments may be biased if those without data differ systematically from those with data. There is not enough information in the record to determine whether missingness occurred or how it was addressed.

Analysis populations are also not described. The registry lists enrollment as 20, while the brief summary describes a plan to enroll 40 consecutive patients. The record does not clarify actual enrollment or identify the participants included in endpoint analyses. No assumptions about inclusion, exclusions, or analysis populations can be made from the available reporting.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The safety listing identifies a group labeled “CEUS-Single Arm.” It reports 20 participants at risk for serious adverse events and 0 affected. The same listing reports 20 participants at risk for other adverse events and 0 affected, with deaths recorded as 0. These are the posted safety figures; they should be read as counts in the registry entry, not as evidence that an event was impossible or that the intervention has no risks.

The registry record does not provide event descriptions, event definitions, severity details beyond the serious-event category, or a safety follow-up period. It does not explain how events were collected or whether events outside the recorded categories were monitored. The “Same day outcome” timeframe belongs to the primary endpoint and should not be assumed to define safety follow-up.

In general, an observed count of zero means no events were recorded in the stated group for the reporting period. It does not establish that the underlying risk is zero, particularly when the group is limited in size or the observation period is unclear. These figures also do not establish that an event, if it occurred, would or would not be caused by the imaging intervention. The registry record does not report a causal safety analysis.

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

The registry record supports a limited but useful description of the research question. The study evaluated CEUS for endoleak detection after EVAR, described CTA as the practice standard, and identified interobserver variability and diagnostic accuracy as aims. The primary endpoint definition and same-day timeframe are also stated. The study is marked completed.

These registry entries do not show how CEUS performed. The registry record does not report the primary endpoint count, reader agreement, sensitivity, specificity, or the number and types of endoleaks detected. It also provides no confidence intervals or other uncertainty estimates. Thus, the posted record cannot establish the direction, size, or precision of any diagnostic result.

The record should not be interpreted as a randomized comparison of treatments. No randomized allocation is reported, and the described procedures are imaging assessments. The comparator role of CTA concerns the evaluation of test findings, not an intervention-control contrast. The safety figures are counts as recorded and do not provide a basis for causal claims about harms.

The difference between the registry enrollment of 20 and the summary’s plan to enroll 40 consecutive patients remains unresolved. This makes the actual study population unclear from the available entry. The absence of analysis methods and results further limits evaluation of how the study addressed its stated aims.

In general, a completed registry entry can document study objectives and selected outcome information without presenting a complete statistical report. For this record, the available details describe the question and some design features, but do not permit a reader to judge diagnostic accuracy, observer consistency, or the precision of findings. No conclusion about clinical benefit or lack of benefit follows from the record alone.

14. Why This Trial Matters Statistically

This study raises a statistical question that is different from comparing treatments: whether an imaging method identifies a finding consistently and how its classifications compare with a reference method. That distinction matters because interobserver agreement, diagnostic accuracy, and the count of participants meeting an endpoint are related but non-interchangeable quantities.

For CEUS to be evaluated as described, the reader needs information on both the imaging classifications and their relationship to CTA. Reader-level results are also needed to assess variability. Without those data, the stated objectives cannot be assessed statistically, even though the endpoint definition and general comparison are described. A clear endpoint definition is a necessary starting point, but it is not a substitute for reporting results and uncertainty.

The enrollment discrepancy also illustrates why consistent reporting matters. The registry lists 20 participants, while the brief summary describes a plan to enroll 40. Without an explanation, readers cannot confidently identify the final study size or judge how many assessments may have contributed to analyses. The record also does not identify analysis populations or handling of missing and indeterminate findings.

Finally, the safety counts need context: the record reports no affected participants in the listed categories, but does not state the safety observation period or provide event-level detail. Statistical interpretation depends on the definitions, denominators, data availability, and analysis procedures behind the numbers. This entry documents the intended diagnostic investigation, while leaving important elements of its empirical interpretation unavailable.

15. 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 limitation for interpreting this trial-specific record is the absence of posted outcome results. Although a primary endpoint is defined, its observed count is not reported. The record also omits the results for interobserver variability, sensitivity, specificity, and endoleak characterization. Without estimates and uncertainty measures, the study’s findings cannot be evaluated for magnitude or precision.

Enrollment is inconsistent across the registry entry: the listed enrollment is 20, whereas the brief summary states that 40 consecutive patients would be enrolled. The reason for this difference and the final analyzed population are not reported. The record does not provide participant flow, image availability, withdrawals, exclusions, or missing-data handling.

There is limited detail on the implementation of the imaging comparison. The record does not state the number of readers, whether assessments were independent or blinded, how disagreements were resolved, or how indeterminate findings were treated. It also does not identify the statistical measure used for agreement or provide the paired results needed to assess CEUS relative to CTA.

The statistical plan is not reported in the registry record. It does not describe adjustment, analysis populations, multiplicity handling, sample-size justification, or interim analyses. Safety reporting is limited to counts without event definitions, descriptions, or a stated safety follow-up period. These omissions constrain interpretation of this specific entry; they do not establish that the information was not collected elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Contrast-Enhanced Ultrasound to Detect Endoleaks After Endovascular Aortic Aneurysm Repair — NCT01005212.
• Registry record last updated 2024-04-12; status last verified 2023-10.
• Results first posted 2024-04-12.
• 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.

19. Record Summary

The registry record identifies a completed cross-sectional evaluation of CEUS for detecting endoleaks after EVAR, with CTA described as the practice standard. The primary endpoint is a participant count defined by persistent pulsatile intrasac color flow outside the stent-graft, with a same-day timeframe. The brief summary describes ultrasound with and without contrast and CTA at the first follow-up visit.

The registry lists enrollment as 20, while the summary describes a plan to enroll 40 consecutive patients. The record does not explain this difference. It reports no statistical analyses and does not provide the primary outcome result, agreement estimate, diagnostic accuracy estimates, or confidence intervals. Safety counts list 0 serious adverse events, 0 other adverse events, and 0 deaths among the stated groups. The entry describes the study question but does not provide enough results or methods detail to assess the diagnostic findings or their precision.