Pharmacological Effects of Crushing Prasugrel in STEMI Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacological Effects of Crushing Prasugrel in STEMI Patients (NCT02212028), a randomized phase 4 study. The primary outcome is P2Y12 Reaction Units (PRU).

2. Clinical Question

The registry describes a prospective randomized study and a hypothesis that the crushed formulation might produce more prompt and enhanced platelet inhibitory effects. The reported primary endpoint is a single time point, 2 hrs after the loading dose. The registry record does not report clinical outcomes as the primary question, and the posted result should be interpreted as a pharmacodynamic comparison rather than evidence about recurrent ischemic events or other patient outcomes.

3. Trial Design

This was a Phase 4, randomized, parallel-group trial with no masking reported. The registry lists University of Florida as the sponsor and describes the study as completed. The record gives a start of 2014-10, a primary completion of 2015-08, and an enrollment of 52.

Participants were randomized to receive either prasugrel 60 mg as crushed tablets or prasugrel 60 mg as whole tablets. The randomized contrast therefore concerns the formulation of the loading dose, rather than a comparison between different drugs. The brief description places the study in patients with STEMI undergoing primary PCI. The record does not give further details about how treatment was administered during PCI or about subsequent treatment.

The primary endpoint was PRU at 2 hrs after loading-dose administration. The registry defines the primary analysis population as participants who received randomized treatment and had a valid primary endpoint value. The arm-level results list 26 participants for the crushed formulation and 24 for whole tablets. These endpoint counts should not be confused with total enrollment, which the record lists as 52.

The brief description says pharmacodynamic testing was planned at several time points, and the registry lists Platelet Reactivity Index (PRI) as a secondary outcome. Results for that secondary outcome are not reported in the registry record. Other details that would clarify implementation—including the sequence and timing of any additional measurements—are 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.

Before assignment: 45 patients did not meet study entry criteria, while 78 provided their written informed consent to participate in the study and, of these, 52 were randomized. the remaining subjects were not randomized because of exclusion criteria emerged after consenting.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary population was defined as patients who received the randomized treatment and had a valid primary end point value (PRU at 2 hours) and was considered for analysis of all endpoints.

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: Two patients in the whole tablets arm were excluded from the analysis because of missing data for the primary end point.

6. Primary Endpoint

The registry lists the primary outcome as P2Y12 Reaction Units (PRU), measured over 2 hrs.

The primary endpoint was P2Y12 Reaction Units (PRU), measured using VerifyNow P2Y12 at 2 hrs after the loading dose. It is a continuous measure of platelet reactivity, and the registry reports arm-level least-squares means with 95% confidence intervals. The stated primary comparison concerns the PRU values for participants assigned to crushed prasugrel and whole-tablet prasugrel.

As a general statistical matter, a pharmacodynamic measure can capture a biological response to treatment without directly measuring a clinical event. PRU is used to quantify platelet reactivity in the study’s specified assay. A group difference in PRU describes a difference in this measurement at the stated time point; by itself, it does not establish a difference in clinical outcomes.

The choice of a fixed measurement time makes the endpoint a comparison at 2 hrs, rather than a summary of the entire course of platelet response. The brief description mentions pharmacodynamic testing at several time points, but only the primary endpoint result at 2 hrs is reported in the registry record. Details about assay performance, measurement variability, and interpretation thresholds are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous endpoint, PRU, summarized as a least-squares mean for each arm and analyzed using ANOVA. The primary time point is 2 hrs after loading-dose administration. The key statistical task is to estimate how the endpoint differs between the randomized formulation groups and to quantify uncertainty around that estimate.

What does a least-squares mean represent?

In general, a least-squares mean is a model-based estimate of a group mean. Depending on the model, it can reflect adjustments for included terms. The registry record does not identify the model terms or covariates used for the reported least-squares means, so it is not possible to determine from the record whether or how they were adjusted. The estimates should be understood as the values reported by the registry rather than as raw arithmetic averages.

How should the confidence interval be read?

In general, a confidence interval conveys the uncertainty of an estimate under the assumptions of the analysis. The PRU confidence intervals reported for the arms describe uncertainty around their respective least-squares means. The reported 95% confidence interval for the mean difference describes uncertainty around the contrast estimated by the ANOVA. It does not describe the range of responses expected for individual participants, and it does not guarantee that the true value lies within the interval.

The interval is useful alongside the point estimate because a single estimate does not communicate precision. A wider interval indicates less precision than a narrower interval on the same scale. The registry’s reported interval for the mean difference spans 10 to 126 PRU units. The endpoints of that interval reflect uncertainty under the reported model; they should not be interpreted as separate treatment effects or as a prediction interval.

What does the p-value add?

In general, a p-value evaluates the compatibility of the observed data with a specified null hypothesis under a statistical model. The registry reports p = 0.022 for the ANOVA comparison. This value does not measure the size or clinical importance of a difference, and it is not the probability that the null hypothesis is correct. Interpretation depends on the planned analysis, the assumptions of the model, and whether other tests were considered.

ANOVA is a method for comparing means using a model-based estimate of variation. In a two-group setting, its central comparison concerns whether the group means differ, subject to the model’s assumptions. The registry record does not provide the ANOVA specification, diagnostic checks, or details about distributional assumptions. It also does not report whether adjustments were made for any covariates or other factors.

Why can variability and over-dispersion matter?

General statistical context: when observations vary more than a model assumes, standard errors can be understated and confidence intervals can be too narrow. This is often described as over-dispersion in settings with a variance structure that permits it. For a continuous endpoint such as PRU, the relevant concern is whether the model adequately represents the outcome’s variability and any dependence among observations. The record does not report evidence of over-dispersion or a specific assessment of variance assumptions; no conclusion about such problems can be drawn from the registry entry.

Randomization supports a comparison between assigned groups by reducing systematic differences in expectation, but it does not remove uncertainty from a finite sample or guarantee balance in every participant characteristic. The record identifies the design as randomized and parallel, but does not report the randomization sequence method, concealment procedures, or baseline characteristics in the registry record for this analysis. No further claims about those design features are warranted.

What can planning calculations tell readers?

General statistical context: sample-size planning asks how many participants would be needed under stated assumptions to target a chosen power for detecting an effect at a specified significance level. Such calculations depend on the effect size, variability, allocation, and statistical assumptions. The registry’s planning description characterizes its illustrations as based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; it also says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not observed power and not evidence that the trial was designed around those assumptions.

Specific participant-per-arm planning values are not reported in the registry record. The record also does not report a sample-size justification for the trial’s original design. A planning illustration based on an observed effect is retrospective and should not be confused with a prospective justification or with the probability that the completed study detected a real effect. The trial’s enrollment of 52 is the registered enrollment figure, not a substitute for a documented design calculation.

The record does not report interim analyses, a stopping rule, or a detailed statistical analysis plan. These omissions limit the ability to assess whether the reported test was the only planned analysis or how analytical decisions were made. They do not change the numerical result reported, but they constrain how completely it can be evaluated.

10. Analyses Reported by the Sponsor

The registry reports an ANOVA analysis of final values with a mean difference of 68, a 95% confidence interval from 10 to 126, and p = 0.022. This is the inferential comparison recorded for the primary endpoint. The arm-level estimates are 95 for crushed prasugrel and 164 for whole tablets, each reported with a 95% confidence interval.

No separate recalculated two-arm contrast is reported in the registry record. The stated reason is that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Accordingly, there is no independent recalculated estimate to set beside the registry’s ANOVA result. The registry record does not flag a discrepancy between its reported analysis and a recalculation.

The recorded ANOVA result should be interpreted using the contrast definition, model specification, and analysis population described by the registry. The population is defined as participants who received randomized treatment and had a valid PRU at 2 hours. Details about contrast coding and model terms are not reported in the registry record. The arm estimates provide context for the direction of the observed values, while the reported mean difference, interval, and p-value summarize the registry’s inferential analysis.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists PRU at 2 hrs as the primary endpoint and Platelet Reactivity Index (PRI) as a secondary outcome. The brief description also refers to pharmacodynamic testing at several time points. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or rules for interpreting multiple endpoints or time points. It is therefore not possible to determine whether or how the reported p-value accounts for other planned comparisons.

Multiplicity is a general statistical concern when several hypotheses are tested: the chance of at least one apparently unusual result can increase as the number of tests grows, depending on the testing strategy. Adjustment procedures and prespecified testing sequences can address this in different ways. No such procedure is reported in the registry record, so the primary p-value should be read as the result attached to the reported primary comparison, without assuming a particular correction or testing hierarchy.

The analysis population was defined as participants who received randomized treatment and had a valid primary endpoint value. That definition identifies who was considered for endpoint analyses, but the registry record does not describe the handling of missing PRU values, the reasons for missingness, or any imputation or sensitivity analyses. The arm-level primary endpoint counts are 26 for crushed tablets and 24 for whole tablets; the registry lists enrollment as 52. The record does not explain the difference between enrollment and the endpoint analysis counts.

The record does not report whether an intention-to-treat analysis, a per-protocol analysis, or another population was used in addition to the stated primary population. It also does not report interim analyses or a detailed statistical analysis plan. Consequently, the available information does not permit a full assessment of missing-data assumptions, sensitivity to participant exclusions, or the prespecification of all analyses.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry lists serious adverse events for 26 participants at risk in each arm, with 0 serious events recorded in the crushed-prasugrel arm and 0 in the whole-tablet arm. For other adverse events, 26 participants are listed at risk in each arm; 1 event is recorded for crushed tablets and 0 for whole tablets. These are the counts in the registry record, not a basis for inferring a safety difference.

The death entries are null, so deaths are not reported in the registry record. The record also lists no top serious adverse-event terms. A zero count in these entries means no events were recorded for that category in the registry results; it does not establish that no event could occur or that the formulations have equivalent safety.

General statistical context: uncommon events are difficult to characterize precisely in a small study, and event counts alone do not establish comparative risk. The registry does not report additional detail about event definitions, severity grading, follow-up duration, or the relationship of events to treatment. The safety counts should therefore be read descriptively and within the limits of the information recorded.

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

The posted primary result describes PRU at 2 hrs after a 60 mg loading dose of prasugrel in patients with STEMI undergoing primary PCI. The crushed-tablet arm had a reported least-squares mean of 95, while the whole-tablet arm had a reported mean of 164. The registry’s ANOVA result gives a mean difference of 68, with a 95% confidence interval from 10 to 126 and p = 0.022. These figures describe the measured endpoint and its estimated group contrast.

The result does not establish that one formulation changes clinical outcomes. PRU is a pharmacodynamic measurement, and the registry’s primary comparison is not a comparison of recurrent ischemic events, survival, or another clinical endpoint. Nor does a measurement at 2 hrs establish the duration of any observed difference. The record’s brief description mentions additional pharmacodynamic testing, but results for those time points are not reported in the registry record.

The trial was randomized, which is relevant to interpreting group comparisons, but the registered enrollment was 52 and the primary analysis population required a valid endpoint after treatment. The available record does not explain the endpoint counts, describe missing-data handling, or report a detailed analysis plan. Those gaps limit assessment of how sensitive the estimate may be to analysis choices or missing observations.

A confidence interval represents uncertainty in the estimated group contrast under the model; it is not a range of individual responses or a guarantee about future results. The p-value does not establish the probability that the observed difference is real, nor does it tell readers whether the difference is clinically important. The record does not provide a threshold for clinically meaningful PRU change. Any interpretation should remain specific to this measurement, this time point, and the reported analysis.

14. Why This Trial Matters Statistically

This trial addresses a statistical question about how formulation relates to a measured biological response after a loading dose. Because the groups received the same drug and dose but different formulations, the randomized contrast is focused on crushed versus whole prasugrel tablets. That makes the endpoint comparison more specific than a comparison of different drugs or doses.

The result also illustrates why estimates and uncertainty should be read together. The registry reports group-level PRU estimates, a mean-difference estimate, a confidence interval, and a p-value. The confidence interval communicates that the reported contrast is uncertain, while the p-value reflects the compatibility of the data with a null hypothesis under the analysis model. Neither statistic alone answers whether the difference matters clinically.

The distinction between a pharmacodynamic endpoint and a clinical outcome is important. PRU measures platelet reactivity using the specified assay. A result on this measure is not a direct estimate of recurrent ischemic events or other patient outcomes. Statistical interpretation should therefore keep the endpoint’s scope in view rather than extending the result to outcomes the primary analysis did not measure.

The record also demonstrates how trial conclusions depend on the analysis population and reporting detail. The primary population required treatment receipt and a valid PRU result, while the record does not detail missing endpoint values or the full analysis plan. Such details help readers assess the robustness and reproducibility of an analysis. The randomized design and reported estimate are informative, but the available record leaves questions about analysis implementation and broader outcome interpretation unresolved.

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 registry record describes the primary analysis population as participants who received randomized treatment and had a valid PRU value at 2 hours. It does not explain why the arm-level endpoint counts are 26 and 24, despite an enrollment of 52, or state how participants without a valid measurement were handled. Reasons for missing endpoint data and sensitivity analyses are not reported in the registry record.

Details needed to reproduce the inferential analysis are limited. The record names ANOVA but does not report model terms, covariate adjustment, variance assumptions, diagnostic checks, or contrast coding. It also does not provide a detailed statistical analysis plan, information about interim analyses, or a multiplicity procedure. The interpretation of the reported p-value in relation to any additional outcomes or measurement times is therefore limited.

The primary result concerns a single measurement at 2 hrs. Although the brief description refers to testing at several time points, the results for those other measurements are not reported in the registry record. The secondary outcome PRI is listed, but its results are not reported in the registry record. The record also does not provide a clinical outcome comparison as the primary result.

Safety information is sparse: the registry gives adverse-event counts, while deaths are not reported in the registry record. Event definitions, follow-up duration, and treatment relatedness are not described in the registry entries. These limits mean the posted results can be interpreted as the reported pharmacodynamic comparison and descriptive adverse-event counts, but they do not resolve questions about durability, clinical outcomes, or broader safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacological Effects of Crushing Prasugrel in STEMI Patients — NCT02212028.
• Registry record last updated 2016-12-28; status last verified 2015-08.
• Results first posted 2016-12-28.
• 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

NCT02212028 is a completed Phase 4 randomized parallel-group study sponsored by University of Florida. It enrolled 52 participants and compared a 60 mg crushed prasugrel loading dose with a 60 mg whole-tablet loading dose in patients with STEMI undergoing primary PCI. Masking was not used.

The primary endpoint was PRU measured with VerifyNow P2Y12 at 2 hrs. Reported least-squares means were 95 for crushed tablets and 164 for whole tablets. The registry reports an ANOVA mean difference of 68, with a 95% confidence interval from 10 to 126 and p = 0.022. PRI is listed as a secondary outcome, but its results are not reported in the registry record. Serious adverse-event counts were 0 in each arm; other adverse-event counts were 1 for crushed tablets and 0 for whole tablets. Deaths are not reported in the registry record.