Predictors of AAA Expansion and/or Rupture: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Predictors of AAA Expansion and/or Rupture (NCT03231397), a randomized phase 4 study. The primary outcome is Standard Uptake Value (SUV).

2. Clinical Question

3. Trial Design

NCT03231397, titled “Predictors of AAA Expansion and/or Rupture,” was registered as a phase 4, randomized, unmasked, factorial study sponsored by Washington University School of Medicine. The recorded start date is 2017-08-01, and the primary completion date is 2020-04-30. Its status is terminated. The registry lists enrollment as 2.

The planned groups were controls without aneurysmal disease, people with small AAAs, people with rapidly expanding AAAs, and people with AAAs undergoing treatment. Each arm description planned six subjects. The control group was described as having atherosclerosis by standard clinical criteria but no aneurysmal disease. Small AAAs were described as having a diameter of 3.0-4.5cm. Rapid expansion was described as >0.5cm over 6 months and/or >1.0cm over 12 months. The treatment-indicated group was described using size thresholds of AAA >5.5cm for males and AAA >5.0cm for females.

The registry states that recruitment was difficult and that the study enrolled one subject with a small AAA and one with a rapidly expanding AAA. It also states that the number of subjects in each category was insufficient to provide meaningful outcomes. No enrollment in the control or treatment-indicated groups is reported. The registry does not explain how randomization was implemented, what the factorial components were, or how participants were assigned to imaging procedures. The unmasked designation indicates that masking was not used; further details of who knew assignments are not reported in the registry record.

The study intended to use PET-CT imaging with 18F-FDG and 11C-PBR28, and to compare imaging findings with mechanical properties assessed through FEA. It also listed rupture potential and a qualitative comparison of SUV and RPI as secondary outcomes. The registry does not report completed outcome analyses or results for these planned comparisons.

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.

Before assignment: The plan was to enroll 30 subjects, however, due to the lack of willing participants, we were only able to enroll 2 subjects.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Recruitment was difficult. We enrolled 1 subject with a small AAA and 1 subject with a rapidly expanding AAA, however, we were unable to recruit the number of subjects in each category to provide meaningful outcomes.

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: We were unable to enroll subjects in the control group and the AAA's undergoing treatment who met the inclusion/exclusion criteria.

6. Primary Endpoint

The registry lists the primary outcome as Standard Uptake Value (SUV), measured over 1 day.

The primary endpoint was Standard Uptake Value (SUV), described in the registry as a measure of aortic inflammation demonstrated by radiotracer uptake. Its timeframe was 1 day. In general, an uptake measure provides a way to quantify the signal from a radiotracer in imaged tissue. The rationale described for this study was to use PET-CT imaging to assess inflammation in the aortic wall and compare the information from 18F-FDG and 11C-PBR28.

The research plan also connected inflammation imaging with mechanical properties of the AAA wall assessed through FEA. That combination was intended to explore potential predictors of aneurysm expansion or rupture. This rationale describes the intended scientific question; it does not establish that SUV predicts either outcome.

The registry does not report a numerical SUV result, a unit, a dispersion measure, or a comparison between the radiotracers. It also does not provide a completed estimate of the relationship between SUV and wall mechanics, aneurysm growth, or rupture. The recorded timeframe identifies when the endpoint was to be assessed, but details of the measurement procedure and analysis are not reported in the registry record. Given the stated recruitment shortfall, the registry explicitly says that the enrolled subjects did not provide meaningful outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are difficult to assess because the registry does not report a completed outcome analysis. It records the study as randomized and factorial, but does not describe the allocation process, factorial factors, analysis model, or a statistical analysis plan. The following concepts are general explanations, not claims about methods that were used in this study.

What does randomization contribute?

In general, randomization assigns participants to study conditions using a chance-based procedure. When implemented and retained appropriately, it can reduce systematic differences between comparison groups at the point of assignment. The registry's randomized designation does not, by itself, show how assignments were generated, concealed, or carried out. Those details are not reported in the registry record. With the very limited enrollment described, the record also does not provide outcome estimates that would permit an assessment of balance or treatment contrasts.

What does a factorial design mean?

In general, a factorial design evaluates more than one intervention or factor within a study, often allowing investigators to assess separate effects and potentially interactions. An interaction asks whether the effect associated with one factor changes according to the level of another factor. The record labels the design factorial but does not identify the factors, their levels, or the allocation structure. It is therefore not possible to determine what factorial effects were intended or whether they were estimated.

How should an endpoint estimate be read?

In general, an estimate describes the observed quantity or contrast, while a confidence interval describes the range of values compatible with the data and the assumptions of the method. Wider intervals indicate less precision. A p-value, when reported, summarizes how inconsistent data are with a specified null model; it does not measure the size or importance of an effect. The registry does not report an SUV estimate, a confidence interval, or a p-value, so none of these features can be evaluated for the primary outcome.

SUV is described as radiotracer uptake representing aortic inflammation. To compare tracers statistically, an analysis would need to specify the relevant observations and contrast, account for the study design, and describe the measurement and model assumptions. The record does not say whether comparisons were paired, independent, adjusted, or based on another structure. No such choice should be inferred from the study aims alone.

Why does sparse data matter?

In general, estimates based on very little information are highly uncertain, and some statistical methods may not be estimable when groups or outcomes have too few observations. A small data set can also make model assumptions difficult to examine. Here, the registry says recruitment was insufficient for meaningful outcomes and reports no analyses. That precludes interpreting the study as having produced a reliable comparative estimate. It would not be appropriate to treat the lack of a reported difference as evidence of equivalence or no association.

The study also describes outcomes related to rupture potential and a qualitative comparison of SUV and RPI. A qualitative comparison may be descriptive rather than a formal test, but the exact planned approach is not reported. For a clinical event outcome, time-to-event methods may be useful in general when follow-up duration and event timing are available. The registry does not provide an event-time analysis or a reported time-to-event estimate.

What does a planning calculation represent?

In general, a sample-size calculation estimates the amount of information needed to detect a prespecified effect under stated assumptions. The registry describes planning assumptions based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also distinguishes total events for time-to-event calculations from participants per arm for other calculations. These are planning conventions, not results from an analysis of the trial. The registry does not report a single comparison reduced to an observed effect, and it does not report an outcome analysis. Accordingly, no such illustration should be read as observed power or as a finding about this trial.

The registry does not report interim analyses, missing-data procedures, adjustments for multiple comparisons, or a prespecified analysis population. These absences limit assessment of the statistical plan as well as interpretation of the recorded outcomes. In general, a transparent report would describe those choices alongside the outcome estimates and their uncertainty; the registry record does not include that level of analysis detail.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary outcome of SUV and secondary outcomes of Rupture Potential Index (RPI) and a qualitative comparison of SUV and RPI. It also describes comparisons between 18F-FDG and 11C-PBR28 and across AAA categories. The registry does not report which comparisons were designated as primary inferential contrasts, whether the secondary outcomes were confirmatory or exploratory, or how multiple comparisons were to be handled. Any multiplicity adjustment or hierarchy of tests is not reported in the registry record.

Missing-data methods are also not reported. The record describes enrollment in the small AAA and rapidly expanding AAA groups, but does not report endpoint completion, participant-level follow-up, or whether any measurements were missing. It would therefore be inappropriate to assume complete outcome data or to infer how missing values were handled.

The analysis population is not specified. The registry does not say whether analyses were intended to follow randomization assignments, include only participants with completed imaging, or use another population definition. No statistical analyses are listed, and there are no outcome estimates from which to determine how participants entered an analysis.

In general, multiplicity matters when several outcomes or contrasts are tested because the chance of at least one apparently notable result can increase across tests. Missing-data methods matter because conclusions can depend on why measurements are absent and how the analysis addresses that absence. These are general considerations; the record does not provide enough information to determine whether or how either issue affected this study.

11. 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 registry lists serious adverse events, other adverse events, and deaths by group. In the Control Group, the recorded counts at risk and affected are zero for serious and other adverse events, and deaths are recorded as zero. The same zero counts are listed for AAA's Undergoing Treatment. The safety listing records one participant at risk in each of the Small AAA's and Rapidly Expanding AAA's groups; in each group, serious adverse events affected zero, other adverse events affected zero, and deaths were recorded as one.

These are registry counts, not an explanation of events. The record does not report causes of death, timing, relationship to imaging or study procedures, or additional clinical context. It also does not describe how adverse events were collected or attributed. The death entries therefore cannot be interpreted as evidence about causation or comparative risk.

For groups with zero participants recorded at risk, zero affected events do not constitute safety observations among enrolled participants. The small recorded at-risk counts in the other groups also leave little basis for estimating event frequency or comparing groups. The entries should be read as sparse descriptive counts, not as a statistical safety analysis.

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

The registry establishes that the study was intended to examine PET-CT radiotracer uptake, AAA wall mechanical properties, and possible predictors of aneurysm expansion or rupture. It also documents a randomized, unmasked, factorial design designation, a primary SUV outcome, and planned secondary outcomes involving RPI. Most importantly for interpretation, the registry states that recruitment was difficult, records enrollment as 2, and says that recruitment was insufficient to produce meaningful outcomes.

The record does not establish whether 18F-FDG or 11C-PBR28 provided more useful or reliable information. It does not provide a primary outcome estimate, a tracer comparison, or a quantitative relationship between inflammation and wall mechanics. It also does not establish that SUV or RPI predicts AAA growth or rupture. Those questions were part of the study rationale, not reported findings.

The absence of reported results is not evidence that the tracers are equivalent, that inflammation is unrelated to AAA behavior, or that a predictor has no value. It means that the registry record does not provide an analyzed result with which to answer those questions. Likewise, the listed safety counts do not establish that a study procedure caused or did not cause any event.

For statistical interpretation, the distinction between a planned question and an estimated result is essential. A study may specify informative hypotheses and outcome measures while still ending without enough data to estimate them meaningfully. The posted record supports a conclusion about the limitations of the available evidence: it documents an intended investigation that did not report interpretable outcome analyses. It cannot support conclusions about clinical use or individual care.

13. Why This Trial Matters Statistically

This study matters statistically because it illustrates the gap between a scientifically motivated design and an estimable analysis. The research question links two kinds of measurement: radiotracer uptake as an indicator of inflammation and FEA-based assessment of aortic wall mechanical properties. The investigators also planned to consider whether these measures could inform understanding of expansion or rupture. Answering those questions requires collected, analyzable measurements and a sufficiently clear description of the comparisons.

The registry records enrollment as 2 and explicitly attributes the lack of meaningful outcomes to recruitment difficulty and insufficient recruitment across categories. This is not merely a limitation on precision around an otherwise reported effect: the record contains no primary outcome estimate or statistical analysis to interpret. The distinction matters because a reader cannot evaluate the size, direction, or uncertainty of an unreported comparison.

The design labels also highlight the need for transparent methods. Randomization and a factorial structure can support useful comparisons when their implementation and analysis are specified. Here, the registry does not describe the allocation procedure or identify the factorial components, so readers cannot reconstruct the intended estimands from the design labels alone.

Finally, the sparse safety counts show why denominators and context are essential. Counts in groups with no participants at risk do not provide observed safety experience, and counts in groups with very limited enrollment cannot support a stable comparative estimate. The statistical lesson is not a conclusion about the tracers or AAA predictors, but the importance of recruitment, clear analysis plans, and complete outcome reporting for turning a research question into evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is the recruitment shortfall documented by the registry. Enrollment is recorded as 2, comprising one subject with a small AAA and one with a rapidly expanding AAA. The registry states that the number of subjects in each category was not sufficient to provide meaningful outcomes. The planned control and treatment-indicated groups have no enrollment reported.

No primary or secondary outcome estimates are reported, and no statistical analyses are listed. The registry does not report SUV values, variability, confidence intervals, or comparisons between tracers. It also does not report results for RPI, the qualitative SUV-RPI comparison, mechanical properties, aneurysm expansion, or rupture. As a result, statistical precision and the direction or magnitude of any association cannot be assessed.

Important design and analysis details are absent from the registry record. These include the randomization procedure, the meaning of the factorial structure, the planned contrasts, the analysis model, the analysis population, handling of missing data, and any multiplicity strategy. The registry does not report interim analyses or a statistical plan. The specific imaging and FEA procedures used for completed participants are not described in the reported outcomes.

The safety entries are limited to group counts and do not include event descriptions, causes, timing, or relatedness to study procedures. In addition, zero participants at risk in some groups means their zero event entries should not be interpreted as observed safety data from enrolled participants.

These limitations arise from what the registry reports and should not be filled in by assumptions about what may have been planned or performed. The record supports describing the study aims and recruitment outcome, but not estimating the performance of the imaging measures or drawing conclusions about AAA predictors.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Predictors of AAA Expansion and/or Rupture — NCT03231397.
• Registry record last updated 2021-07-09; status last verified 2021-06.
• Results first posted 2021-07-09.
• 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.

18. Record Summary

NCT03231397 was a phase 4, randomized, unmasked, factorial study sponsored by Washington University School of Medicine, with a recorded start date of 2017-08-01 and primary completion date of 2020-04-30. Its status is terminated, and enrollment is recorded as 2.

The study aimed to compare 18F-FDG and 11C-PBR28 PET-CT imaging measures of aortic inflammation and relate imaging to AAA wall mechanical properties assessed through FEA. The primary outcome was SUV, with a timeframe of 1 day. Secondary outcomes included RPI and a qualitative comparison of SUV and RPI.

The registry reports one enrolled subject with a small AAA and one with a rapidly expanding AAA. It states that recruitment was difficult and insufficient to provide meaningful outcomes. No outcome analyses or estimates are reported, so the record does not establish tracer differences or predictors of expansion or rupture.