STAT-STatin and Aspirin in Trauma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for STAT-STatin and Aspirin in Trauma (NCT02901067), a randomized phase 2 study. The primary outcome is Incidence of VTE.

2. Clinical Question

3. Trial Design

STAT was a phase II, pragmatic, prospective, randomized, double-blind, adaptive clinical trial sponsored by Denver Health and Hospital Authority. It used a parallel-group design with quadruple masking. The registry describes the trial as evaluating aspirin and rosuvastatin in patients with fibrinolysis shutdown after trauma, with acute lung injury and venous thromboembolism among its clinical concerns.

The experimental regimen combined 325mg aspirin with 20mg rosuvastatin in a single capsule, administered daily by mouth or feeding tube during the ICU stay. The control group received an identical-looking placebo on the same schedule. The registry reports enrollment of 43 participants. For the primary outcome, results are posted for 19 experimental participants and 18 control participants. The reason the primary-outcome group counts differ from overall enrollment is not reported in the registry record.

The trial started on 2017-02-03, had a primary completion date of 2021-05-24, and is listed as terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the trial ended or whether the planned follow-up was completed. Although the trial is described as adaptive, the adaptation procedures and decision rules are not reported in the registry record. The intended allocation ratio, detailed protocol, and operational definitions beyond the posted outcome descriptions are also not reported in the registry record.

4. Participant Flow and Accounting

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

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 Incidence of VTE, measured over Day 5 or ICU discharge or upon symptoms of VTE (whichever comes first).

The primary endpoint was incidence of venous thromboembolism, expressed as the percentage of patients with an event. The registry specifies screening duplex ultrasound of the legs and central line on day 5, at ICU discharge, or when symptoms of VTE arose, whichever came first. This definition combines scheduled screening with earlier assessment at discharge or symptom onset.

Screening is relevant because a trial endpoint based only on clinically recognized events may not capture events found through planned imaging. Using a stated assessment approach and time point also clarifies what counted as an opportunity to identify VTE. The posted description does not give further detail about diagnostic criteria, how indeterminate imaging findings were handled, or whether outcome assessors adjudicated events; those details are not reported in the registry record.

The primary outcome was reported as 0% in the experimental group and 22% in the control group, with group counts of 0 of 19 and 4 of 18, respectively. These are the observed results under the registry's endpoint definition. The timing rule means the results should be understood in relation to the specified assessment window, rather than as a report of events over an unspecified period.

7. Results Posted in the Registry

• Experimental: 0.0% (0/19) versus 22.2% (4/18) on control; risk difference -22.2 percentage points (95% CI -41.4 to -3.0); unadjusted two-proportion z-test p = 0.030.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

All-cause Mortality

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Experimental: 5.3% (1/19) versus 0.0% (0/18) on control; risk difference 5.3 percentage points (95% CI -4.8 to 15.3); unadjusted two-proportion z-test p = 0.324.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Experimental and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning laboratory measures, clinical events, mortality, and ICU course. These outcomes address different aspects of the trial's clinical question and are not interchangeable with the primary VTE endpoint. The primary result concerns screened VTE incidence under a specified assessment schedule; the secondary outcomes broaden the description of patient outcomes and biological measures.

The posted mortality result illustrates the uncertainty that can accompany sparse binary outcomes: the observed counts were one in the experimental group and none in control, while the reported comparison interval includes zero. It does not confirm or negate the primary VTE pattern. The outcomes differ in definition and timing, and a result for one does not automatically corroborate a result for another.

Secondary outcomes often have less evidential weight than the primary endpoint when many questions are examined. Each additional comparison creates more opportunities for apparently notable findings to arise by chance. Unless the analysis plan accounts for multiplicity, the nominal p-values for secondary comparisons do not necessarily control the overall chance of a false positive across the family of tests. The registry record does not report a multiplicity strategy or a hierarchy for interpreting the secondary outcomes.

The registry lists eight posted secondary results, while the broad outcome list includes multiple measures. Their full results and analysis details should be considered on their own terms rather than compressed into a single overall conclusion. Without reported adjustment procedures, prespecified decision rules, and complete analysis details, isolated secondary findings are best treated as exploratory context. They can help frame questions for further study, but they should not be used to override the primary estimate or to imply a consistent pattern without examining each outcome's data and uncertainty.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Fibrinolysis Phenotypes
• Plasminogen Activator Inhibitor (PAI) - 1 and Tissue Plasminogen Activator (tPA) Levels in Plasma
• Incidence of Acute Lung Injury (ALI)
• Ventilator Free Days
• Incidence of Arterial Thrombotic Complications: Myocardial Infarction (MI) and Cerebrovascular Accident (CVA).
• All-cause Mortality
• Intensive Care Unit (ICU) Days
• Incidence of Multiple Organ Failure (MOF)

9. Statistical Interpretation

10. Statistical Methods Explained

The registry presents a binary primary outcome: whether each participant had VTE detected under the stated assessment schedule. A group percentage expresses the proportion of participants with the event. The posted group values are 0% for the experimental arm and 22% for control; the corresponding counts are 0 of 19 and 4 of 18. With binary outcomes, event counts and their denominators are central to interpretation because they show how much information supports the comparison.

What does a risk difference describe?

A risk difference contrasts the event proportions between groups. A value below zero in the reported experimental-versus-control contrast indicates a lower observed event proportion in the experimental group. The posted estimate is -0.222. This is an absolute contrast, rather than a relative measure such as a risk ratio. It is tied to the trial's population, follow-up assessment, endpoint definition, and observed data.

The registry also reports a confidence interval from -0.414 to -0.030. A confidence interval is a range of values generated by a statistical procedure that, under its assumptions, reflects uncertainty in the estimate. It is not a range containing a known fixed fraction of individual participant outcomes, nor does it assign a probability to the true effect after the data are observed. Its width is informative: wider intervals indicate less precision. With few events, estimates of binary outcomes can be particularly uncertain.

What does the p-value add?

The posted unadjusted p-value for the primary comparison is 0.03. A p-value measures how compatible the observed data, or results more extreme under the test, are with a specified null hypothesis and test assumptions. It is not the probability that the null is true, and it does not measure the size or importance of the observed difference. Interpretation should consider the estimate and confidence interval as well as the p-value. The detailed test or model underlying the primary comparison is not reported in the registry record.

For mortality, the registry separately reports a Fisher Exact analysis with p >0.05. Fisher's exact test is a method for comparing categorical outcomes using the observed counts, commonly useful when event counts are sparse. The posted unadjusted risk difference and p-value for mortality are also given. These are distinct statistical summaries, and the registry does not describe how the analyses relate to one another or identify a primary mortality analysis plan.

Why do the design labels matter?

Random allocation is intended to make treatment groups comparable on average, including with respect to factors that are measured and unmeasured. In a small trial, however, chance differences between groups may remain. A parallel design assigns participants to one group for comparison with the other. Double-blind and quadruple masking describe masking labels, but the registry does not identify which individuals or roles were masked. The title calls the study adaptive, yet the adaptation rules, timing, and decision procedures are not reported in the registry record.

The primary outcome's assessment schedule matters statistically because the opportunity to detect events is part of the outcome definition. Screening at the specified time, discharge, or symptom onset may identify events differently from symptom-based diagnosis alone. Further detail on diagnostic thresholds, missing imaging, and adjudication is not reported in the registry record, so those features cannot be assessed from the posted description.

What can planning calculations tell readers?

Any sample-size illustrations associated with the results are planning exercises, not evidence of observed power. The stated assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such illustrations show how assumptions about the effect to detect and design relate to a planning target. They do not show that the trial had a particular probability of detecting an effect after it was conducted. The registry record does not report the trial's own sample-size justification, so the planning illustrations should not be taken as its original design rationale.

11. Confidence Intervals and Precision

Precision is limited by the small number of primary events. The experimental arm had 0 events among 19 participants, while control had 4 among 18. The estimated risk difference was -0.222, and its 95% confidence interval ranged from -0.414 to -0.030. The interval gives a range of effect values compatible with the data under the method's assumptions; it does not remove uncertainty or make the estimate exact.

The interval excludes zero, consistent with the unadjusted p-value of 0.03. That statistical feature should not overshadow the interval's breadth or the sparse event counts. With few events, one or a small number of additional outcomes can materially change a group proportion and the contrast. The estimate should therefore be read as an uncertain trial result rather than a finely determined measure of effect.

The registry does not report a confidence interval method or detailed model for the primary result, so the construction and assumptions behind the interval cannot be evaluated from the record. It also does not report the analysis population or the disposition of all enrolled participants for this endpoint. These omissions limit assessment of how missing or unavailable assessments may relate to the reported denominators.

For 30-day mortality, the posted risk difference was 0.053, with a 95% confidence interval from -0.048 to 0.153. This interval includes zero and spans both directions of difference. Together with the sparse counts, this means the mortality estimate is also imprecise. Confidence intervals describe uncertainty in estimates; they do not by themselves establish that an outcome is clinically meaningful or rule out differences not resolved by the trial.

12. Multiplicity, Missing Data and Analysis Populations

The registry describes multiple outcomes: the primary VTE endpoint and secondary measures that include fibrinolysis phenotypes, plasma markers, acute lung injury, ventilator-free days, arterial thrombotic complications, mortality, ICU days, and multiple organ failure. Testing several outcomes raises a multiplicity issue. When many statistical comparisons are made, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that family of comparisons.

The registry record does not report whether secondary comparisons were adjusted for multiplicity, whether outcomes were ranked in a testing hierarchy, or whether any were designated exploratory. It also does not report interim analyses, stopping boundaries, or the statistical decision rules associated with the trial's adaptive description. Without these details, the posted p-values should not be read as if they necessarily reflect a single, fully specified testing strategy.

Missing-data handling is also not reported in the registry record. The overall enrollment is 43, while the primary outcome results list 19 experimental participants and 18 control participants. The record does not explain the difference in those counts, report reasons for unavailable primary assessments, or state how missing outcomes were handled. It would be inappropriate to assume that the unlisted participants had no events or to infer why their results are absent.

The analysis population is not reported in the registry record. In particular, the record does not specify whether the primary analysis followed intention-to-treat principles, included only participants with evaluable screening, or used another population definition. The detailed statistical analysis plan, model specification, and prespecified handling of protocol deviations are not reported either. These are important details for judging whether the posted estimates align with the trial's intended analysis and how robust they may be to missing information.

The trial is labelled adaptive, but the nature and timing of adaptation are not reported. That omission prevents assessment of whether any adaptation could affect error rates or interpretation. These gaps do not invalidate the posted results, but they limit independent appraisal of the full analysis strategy.

13. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombocytopenia (5.6%), gastro-intestinal bleeding (5.6%).

The adverse-event summary reports serious adverse events in 0 of 19 experimental participants and 2 of 18 control participants. Other adverse events were reported in 0 of 19 experimental participants and 3 of 18 control participants. The summary also records one death in the experimental group and none in control. These counts describe the posted safety data; they do not establish that an event was caused by the assigned regimen or that no unreported events occurred.

The registry lists thrombocytopenia and gastro-intestinal bleeding among the leading serious adverse-event terms, each reported as 5.6%. The record does not give enough detail in this summary to determine the clinical course, timing, severity beyond the serious-event classification, or relationship to treatment for these terms. Sparse event counts make between-group safety comparisons imprecise.

Safety findings should be read alongside the trial's size, follow-up, event definitions, and missing reporting details. The registry does not report a comprehensive causal assessment or the criteria used to attribute events to treatment. The counts are descriptive and should not be interpreted as proof of comparative safety.

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

The primary result is an observed comparison of VTE incidence in this randomized trial: no events were reported in the experimental group and four in control, with an estimated risk difference of -0.222. The confidence interval, from -0.414 to -0.030, expresses substantial uncertainty around that estimate. The result describes the participants and endpoint assessment reported in this trial; it is not a guarantee of the same pattern elsewhere.

A statistically notable result does not by itself establish the size, importance, or reliability of an effect. The p-value of 0.03 is not the probability that the treatment has no effect, and it cannot account for reporting details that are not available in the registry record. The small event count and unreported analysis-plan details limit how firmly the result can be generalized or interpreted as a definitive estimate.

The result does not establish why the groups differed, whether the difference reflects the combined regimen or another factor, or how aspirin and rosuvastatin would perform separately. The trial compared the combined capsule with placebo; it was not described as a comparison of the two drugs independently. Nor does the primary VTE finding answer the other clinical questions listed in the registry, such as acute lung injury, mortality, or ICU course.

The terminated status is part of the record, but the reason for termination is not reported. It therefore cannot be used by itself to infer the reason for the trial's ending or its impact on results. Likewise, the enrollment count and primary outcome denominators do not reveal why some participants are not represented in the endpoint results.

In summary, the posted data show a lower observed VTE proportion in the experimental group, but uncertainty and reporting limitations remain. This is a description of the trial result, not a clinical recommendation or a conclusive claim about effectiveness.

15. Why This Trial Matters Statistically

This trial is statistically instructive because its primary comparison combines a noticeable observed contrast with a small number of events. Seeing the event counts beside the risk difference and confidence interval helps distinguish the direction of the estimate from the amount of information supporting it. A p-value alone would not convey the breadth of uncertainty or the sensitivity of sparse outcomes to individual observations.

The endpoint also illustrates how outcome ascertainment shapes statistical interpretation. VTE was assessed through screening ultrasound at a scheduled point or earlier under specified conditions. The estimate therefore relates to that detection strategy and timing, rather than to an abstract event rate detached from measurement. Clear endpoint definitions are central to understanding what a group comparison actually represents.

The record also highlights why design labels do not substitute for a detailed protocol. Randomization, masking, and an adaptive design are important features, but readers need allocation procedures, masking roles, adaptation rules, analysis populations, and missing-data methods to assess implementation and analysis fully. Several of those details are not reported in the registry record.

Finally, the presence of numerous secondary outcomes makes multiplicity and selective emphasis relevant statistical concerns. A primary result should be distinguished from a broad set of additional comparisons, particularly when the analysis hierarchy and adjustment strategy are not reported. Taken together, these features make the trial a useful example of reading an estimate in context: event counts, interval precision, outcome definition, design, and reporting completeness all contribute to interpretation.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The posted primary results include fewer participants than the overall enrollment, but the registry does not report why. Reasons for unavailable assessments, endpoint missingness, and the handling of missing data are not reported in the registry record. The analysis population and participant flow are also not specified, limiting assessment of how the reported denominators were formed.

The primary endpoint description gives the screening method and assessment timing but not detailed diagnostic criteria, adjudication procedures, or handling of inconclusive examinations. These details could affect how consistently events were identified. The statistical test or model behind the primary comparison is not stated, and the registry does not provide the full analysis plan.

The trial is described as adaptive, but adaptation procedures and any interim analyses are not reported. The reason for termination is also not reported. These omissions make it difficult to evaluate whether the conduct or analysis followed a prespecified decision framework. The record does not report a multiplicity strategy for the range of secondary outcomes.

The event counts are sparse, and the confidence interval is broad. The findings therefore have limited precision, especially for outcomes with few events. Safety counts are descriptive, and causal attribution and detailed timing are not reported in the safety summary. These limitations are specific to interpreting the posted record; they do not imply that unreported procedures or information were absent from the full trial documentation.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: STAT-STatin and Aspirin in Trauma — NCT02901067.
• Registry record last updated 2023-04-27; status last verified 2023-04.
• Results first posted 2023-04-27.
• 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

STAT was a phase II, randomized, parallel-group, quadruple-masked trial of daily aspirin plus rosuvastatin versus placebo in trauma patients with fibrinolysis shutdown. It enrolled 43 participants and is listed as terminated. The primary endpoint was VTE incidence assessed by screening ultrasound on day 5, at ICU discharge, or when symptoms arose, whichever came first.

Primary results were posted for 19 experimental participants and 18 control participants. VTE was reported in 0 experimental participants and 4 control participants; the risk difference was -0.222, with a 95% confidence interval from -0.414 to -0.030 and an unadjusted p-value of 0.03. The reason for termination, the primary analysis population, missing-data methods, and detailed adaptive procedures are not reported in the registry record.