Aspirin and Enoxaparin for VTE in Trauma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aspirin and Enoxaparin for VTE in Trauma (NCT02396732), a randomized phase 4 study. The primary outcome is Incidence of Venous Thromboembolism.

2. Clinical Question

The clinical question is about the additional contribution of aspirin when enoxaparin is used for thromboprophylaxis after trauma. It is not a comparison of enoxaparin with no preventive treatment. The registry’s stated purpose also included assessing the safety and efficacy of dual thromboprophylaxis, but the primary outcome was the incidence of venous thromboembolism.

The record describes a randomized trial but does not report the detailed eligibility criteria, the method used to generate or conceal assignments, or the basis for selecting the treatment period. Those details are not reported in the registry record. The posted endpoint counts can describe what was recorded in the two groups, but they do not by themselves establish how broadly the findings apply to other trauma patients or settings.

3. Trial Design

This was a Phase 4, randomized, parallel-group trial with no masking reported. The registry lists enrollment of 31 and a status of terminated. The start is recorded as 2016-02, and primary completion as 2018-05-15. The reason for termination and whether it was related to enrollment, safety, resources, or another consideration are not reported in the registry record.

One group received low-molecular-weight heparin (enoxaparin) plus aspirin, while the other received enoxaparin alone. Both regimens were described as continuing after consent until Intensive Care Unit discharge. The posted arm sizes are 14 for the combination group and 17 for the enoxaparin-alone group. The record does not describe additional treatment procedures, adherence, crossover, or treatment discontinuation.

The primary outcome was an event count for venous thromboembolism, with a timeframe of up to 2 months of hospitalization. The definition included newly reported deep vein thrombosis and pulmonary embolism, symptomatic or asymptomatic. Deep vein thrombosis was assessed by venous duplex ultrasonography; pulmonary embolism was assessed by chest computed tomography with angiography or a ventilation-perfusion scan.

Mortality and change in hypercoagulability are listed as secondary outcomes. The registry record does not report the full statistical plan, including a planned sample-size justification, allocation details beyond randomization, or the planned analysis population. It also does not report the reason for early termination or whether a prespecified stopping rule was used. No inference about those design features can be made from the posted outcome counts.

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 Venous Thromboembolism, measured over Up to 2 months of hospitalization.

The primary endpoint is the incidence of venous thromboembolism, recorded as the number of incidents. It includes new cases of deep vein thrombosis and pulmonary embolism, whether symptomatic or asymptomatic. The registry specifies venous duplex ultrasonography for assessing deep vein thrombosis and chest computed tomography with angiography or a ventilation-perfusion scan for assessing pulmonary embolism.

This endpoint addresses the trial’s central clinical question: whether adding aspirin to enoxaparin is associated with a different number of thromboembolic events in the study groups. Counting both symptomatic and asymptomatic events can capture events found through imaging as well as those identified after symptoms. It also means that interpretation depends on how imaging was conducted and how consistently events were sought and classified. Those implementation details are not reported in the registry record.

The stated timeframe is up to 2 months of hospitalization. It is therefore a bounded in-hospital measure, not a report of events across an unrestricted follow-up period. The primary outcome is presented as counts rather than as a time-to-event measure, and the record does not post a comparison estimate or confidence interval for this outcome. The counts can be described, but they do not alone quantify the uncertainty around a treatment-group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the observed data from the uncertainty around them. For this trial, that distinction matters because the primary endpoint is reported as a small count of events, while the registry does not post an inferential comparison for that outcome.

What does an event count show?

A count reports how many endpoint events were recorded in a group. It is a direct description of the posted outcome, but a count alone does not estimate how much the groups differ with quantified uncertainty. Counts can be useful for understanding the scale of the observed data, especially when events are uncommon, but they should not be read as a complete statistical comparison.

The primary endpoint is defined as incidents of venous thromboembolism, not explicitly as the number of participants with at least one event. This distinction can matter in general: an event count and a participant count need not represent the same quantity if repeat events are possible. The registry record does not give further detail about repeat events or how multiple events in one participant were handled. The posted count should therefore be interpreted according to the endpoint as described, without assuming additional counting rules.

Why is there no primary comparison estimate?

The registry indicates that values are missing or not estimable for a two-arm comparison of the primary count outcome. No primary confidence interval or p-value is posted. Without such an estimate, readers cannot use the registry results to quantify the uncertainty around the difference between groups using a reported inferential method. This does not make the observed counts unusable; it means their interpretation should remain descriptive.

A statistical comparison for counts may depend on assumptions about the event-generating process and the form of variability. In general, over-dispersion occurs when observed variation is greater than a chosen model expects. If present, it can make standard errors too small and confidence intervals too narrow unless the method accounts for it. The registry record does not report a count model, a dispersion assessment, or another planned method for the primary outcome, so no such method or assumption should be attributed to this trial.

How should the mortality comparison be read?

The posted mortality comparison uses a risk difference. In general, a risk difference expresses the difference between the proportions experiencing an outcome in two groups, with the direction determined by the stated comparison. The reported estimate is 0.059 for LMWH Alone compared with LMWH + ASA. Its 95% confidence interval runs from -0.053 to 0.171. Because that interval crosses zero, it includes values corresponding to no difference as well as values on either side of zero.

A confidence interval is not a guarantee that the true effect lies inside its endpoints. Rather, it summarizes uncertainty under the method’s assumptions and repeated-sampling interpretation. The interval’s breadth relative to the point estimate signals that the estimate is not precise. The unadjusted p-value of 0.356 is a measure of compatibility between the observed data and a specified no-difference hypothesis under the analysis method. It is not the probability that the hypothesis is true, nor does it demonstrate equivalence or absence of an effect.

“Unadjusted” means the posted p-value is not reported as adjusted for multiple comparisons. That matters when several outcomes or analyses are examined: repeated testing can increase the chance of obtaining at least one small p-value by chance. The record does not report a multiplicity adjustment or a testing hierarchy. This makes secondary p-values exploratory in interpretation unless a prespecified plan says otherwise, and no such plan is reported.

What can planning calculations say?

The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. These are illustrations of sample sizes under stated assumptions, not the study’s original design justification and not observed power. The registry record does not report the trial’s own sample-size justification. A planning calculation based on an observed effect is particularly uncertain when the observed result comes from a small study, because that effect estimate may itself be unstable.

In general, power is a design property defined with respect to an assumed effect, variability, analysis method, and significance level. It is not a measure of whether a completed study “found” an effect. A post hoc calculation using the observed estimate does not resolve the uncertainty in the observed result. Any sample-size illustration should therefore be read as a hypothetical planning aid, not as evidence that the trial was adequately or inadequately powered.

What assumptions remain unreported?

The registry record does not report the full analysis plan, handling of missing data, analysis population, or whether outcome assessment was blinded. It also does not report how the random allocation sequence was generated or concealed. These details can affect the risk of bias and the interpretation of statistical estimates. Their absence from the registry record does not prove that the procedures were not used; it means they cannot be evaluated from the posted information.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a detailed statistical analysis plan describing how the primary and secondary outcomes were to be tested. In particular, it does not state whether a formal hierarchy was planned, whether secondary outcomes were exploratory, or whether any adjustment for multiple comparisons was intended. Without that information, readers cannot determine which analyses were intended to support confirmatory conclusions.

Multiplicity arises when several hypotheses are tested or several outcomes are examined. In general, testing many hypotheses without adjustment can increase the probability of at least one apparently unusual result arising by chance. The mortality p-value is explicitly unadjusted. It should be interpreted in that context, not as though it were necessarily the sole planned test. The record does not report enough detail to judge the total number of statistical tests that may have been considered.

Information about missing outcomes is also not reported in the registry record. There is no detailed account of participants lost to follow-up, unavailable endpoint assessments, exclusions after randomization, or the method used to handle missing observations. The treatment groups have posted denominators, but the record does not explain how those denominators relate to the analysis population or whether every randomized participant contributed to every outcome.

The analysis population is not described as intention-to-treat, per-protocol, or another defined set. The record also does not report whether participants were analyzed according to their original assignment or according to treatment received. These omissions restrict evaluation of the effects of nonadherence, crossover, or post-randomization exclusions. They do not show that any such events occurred; they leave the relevant handling unclear.

The trial is listed as terminated, but the reason and any impact on outcome collection are not reported. No conclusions about missingness, selective reporting, or the timing of analyses can be drawn from that status alone. The absence of these methodological details makes the posted results harder to assess for completeness and prespecification.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bacteremia (23.5%), venous thromboembolism (17.6%), altered mental status (7.1%), pneumonia (7.1%).

The registry posts serious adverse event figures by group, including the number at risk and the number affected. The listed figures are 2 affected among 14 at risk in the LMWH + ASA group and 4 among 17 at risk in the LMWH Alone group. It also posts other adverse event figures of 1 among 14 and 1 among 17, respectively. These counts describe what was recorded in the registry; they do not establish that an event was caused by a study treatment.

Deaths are listed as 0 in the combination group and 1 in the enoxaparin-alone group. Serious adverse events, other adverse events, and deaths are distinct reported categories and should not be combined or treated as interchangeable outcomes. The registry also lists serious adverse event terms and percentages, but does not provide enough accompanying detail to determine how those terms relate to each participant or whether categories overlap.

With small groups, safety counts are descriptive and can be imprecise. The record does not report a formal statistical comparison for these safety figures, event timing, severity grading beyond the serious-event classification, or an attribution assessment. It also does not report a detailed safety analysis plan. The counts should therefore be read as a limited account of recorded adverse events, not as a complete comparative assessment of safety.

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

The registry results show that venous thromboembolism incidents were recorded in both randomized groups during the stated hospitalization timeframe. The primary endpoint is presented as counts, and the registry does not provide an inferential comparison for those counts. The observed data therefore describe the trial experience but do not quantify a reliable difference between the treatment strategies.

The posted mortality analysis is also uncertain. Its point estimate is accompanied by a confidence interval extending across zero and an unadjusted p-value. Those statistics do not demonstrate equivalence, prove that there is no difference, or establish a treatment effect. They indicate that the available data do not estimate the comparison precisely enough to support a firm conclusion.

These results do not establish that adding aspirin does or does not prevent venous thromboembolism. They also do not establish that either regimen is safer, or that the findings apply to trauma patients beyond the population and treatment period represented in this trial. The record does not report enough detail about eligibility, missing outcomes, analysis populations, or the reason for termination to resolve those questions.

In general, a small number of participants and events can leave substantial uncertainty, even when a numerical difference is observed. A non-significant p-value is not proof of no effect, and a favorable-looking count is not proof of benefit. The most defensible reading is limited to the posted descriptive counts and the uncertainty reflected in the available secondary comparison.

The registry status is terminated, but the reason is not reported in the registry record. That status should not be treated as evidence about the direction of the results or the cause of trial closure. Additional information about the trial’s conduct and analysis would be needed to evaluate the findings more fully.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a randomized design and a posted outcome result can still leave substantial uncertainty. Randomization is a design feature intended, in general, to support fair comparisons between groups. But the ability to estimate a treatment contrast precisely also depends on the amount of information in the data, the number of outcome events, and the quality and completeness of outcome measurement.

The primary endpoint is clinically focused and defined to include both deep vein thrombosis and pulmonary embolism. Yet the registry reports only small event counts and no inferential comparison for that primary count outcome. This illustrates why a clear endpoint definition does not by itself supply an estimate of uncertainty. Readers need both the observed data and an appropriate comparison analysis to understand how strongly the results distinguish between plausible effects.

The secondary mortality comparison demonstrates another important point: a point estimate should be read together with its confidence interval and analysis context. The broad interval and unadjusted status matter as much as the point estimate when judging precision. A p-value alone cannot summarize the importance, direction, or certainty of a result.

The terminated status and missing statistical-plan details also show why registry outcomes need context. Without a reported sample-size justification, analysis population, missing-data approach, or reason for termination, it is difficult to evaluate whether the posted analysis reflects the intended design. These are not grounds to assume misconduct or a particular bias, but they are important limits on interpretation.

For biostatisticians and clinical researchers, the record emphasizes the distinction between descriptive evidence and confirmatory inference. It also shows why small trials can be valuable for documenting feasibility and observed outcomes while remaining inconclusive about comparative effects. The registry findings are best understood as limited evidence that requires careful attention to design and reporting uncertainty.

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 number of participants was limited, with 14 in the LMWH + ASA group and 17 in the LMWH Alone group. The primary event counts were also small. Sparse data can make comparisons sensitive to a small number of observations and can limit precision. The registry does not post a confidence interval or p-value for the primary outcome, so the uncertainty around its between-group contrast cannot be evaluated from a reported inferential estimate.

The study is listed as terminated, and the reason is not reported in the registry record. There is no information about whether termination affected recruitment, follow-up, or outcome completeness. The record also does not describe a planned sample-size justification, so it is not possible to assess the original design assumptions or the intended precision.

The trial was unmasked. The record does not explain whether outcome assessment was blinded or whether independent adjudication was used. Because the primary endpoint includes imaging-assessed events, details about assessment procedures and consistency would help readers evaluate possible measurement differences; these details are not reported in the registry record.

Further limitations include the absence of a detailed analysis plan, analysis population definition, missing-data accounting, and reported method for the primary count comparison. The record does not give detailed eligibility criteria, adherence information, crossover details, or the handling of repeat events. These omissions restrict assessment of internal validity and generalizability without establishing that a specific bias occurred.

Finally, secondary outcome information is incomplete, and the posted mortality comparison is unadjusted. The available safety counts are descriptive and do not include a reported comparative safety analysis. Together, these limitations mean that the registry results should be treated as a narrow account of the posted observations rather than a definitive estimate of treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Aspirin and Enoxaparin for VTE in Trauma — NCT02396732.
• Registry record last updated 2019-11-19; status last verified 2019-10.
• Results first posted 2019-11-19.
• 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.

18. Record Summary

NCT02396732 is a Phase 4 randomized, unmasked, parallel-group trial of enoxaparin plus aspirin compared with enoxaparin alone for thromboprophylaxis in trauma patients. The registry lists enrollment of 31, a start of 2016-02, primary completion on 2018-05-15, and status as terminated.

The primary outcome was venous thromboembolism incidents during up to 2 months of hospitalization. Counts were posted for both groups, but a two-arm statistical comparison was not estimable in the registry record. Mortality is listed as a secondary outcome with an unadjusted comparison; change in hypercoagulability is also listed, but a numerical result is not reported in the registry record.

The reason for termination, detailed analysis plan, sample-size justification, analysis population, and missing-data handling are not reported in the registry record. The posted results are therefore descriptive and limited in precision, and they do not establish a comparative treatment effect.