Ticagrelor Administered as Standard Tablet or Orodispersible Formulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ticagrelor Administered as Standard Tablet or Orodispersible Formulation (NCT03822377), a randomized phase 3 study. The primary outcome is Evaluation of Platelet Inhibition.

2. Clinical Question

The central statistical question is about a measured biological response, not a direct measure of clinical benefit. The registry explains that PRU measures platelet aggregation in the presence of a P2Y12 inhibitor and that lower PRU levels are associated with the expected antiplatelet effect. The posted results give a median and interquartile range for each formulation. Those summaries describe the observed distributions, but they do not, by themselves, establish the size or uncertainty of a between-arm difference.

The registry also lists outcomes for insufficient antiaggregation, residual platelet reactivity at various timepoints, clinically relevant bleeding events, and adverse events. These outcomes provide additional context, but the record does not report a sponsor analysis for them. The clinical question should therefore be read alongside the limitations of the posted comparisons and the absence of a reported statistical analysis plan.

3. Trial Design

This was a phase 3 randomized, parallel-group study with single masking. The registry lists 130 participants and identifies the study status as completed. The recorded start date is 2019-06-27, and the primary completion date is 2020-08-31. The sponsor is Azienda Ospedaliero Universitaria di Sassari.

Participants were described as having ST elevation myocardial infarction or very high-risk non-ST elevation myocardial infarction and undergoing primary PCI. The intervention arms received a ticagrelor 180 mg loading dose, either as orodispersible tablets or as standard coated tablets. The registry lists 65 participants in each arm for the primary endpoint. It does not describe who was masked, how randomization was generated or concealed, or whether the treatment assignment could be recognized during administration.

The primary outcome was platelet inhibition measured by VerifyNow one hour after the loading dose. Its posted summaries are the median PRU and interquartile range for each arm. The registry also lists secondary outcomes addressing insufficient antiaggregation, residual platelet reactivity at 2, 4 and 6 hours, and clinically relevant bleeding events at 30 days. The record lists six outcome measures, while three secondary outcomes have posted results.

Although enrollment and arm counts are listed, the registry record does not report whether all randomized participants were included in each analysis, how participants were handled if an outcome was unavailable, or whether the analysis followed intention-to-treat or another population definition. A protocol-level sample-size justification, detailed allocation methods, and the planned statistical analysis are not reported in the registry record. The planning illustrations associated with some posted secondary comparisons are based on observed effects; they are not evidence of the trial's original design rationale.

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 Evaluation of Platelet Inhibition, measured over 1 hour.

The primary endpoint is platelet reactivity one hour after a ticagrelor loading dose, measured using the VerifyNow PRU test. Results are expressed in P2Y12 Reaction Units. The registry explains that the test measures P2Y12 receptor blockade and that PRU reflects the extent of platelet aggregation in the presence of a P2Y12 inhibitor. It also notes that lower PRU levels are associated with the expected antiplatelet effect.

The registry specifies a median and interquartile range as the summary measures. The reported median is 94.0 PRU for orodispersible tablets, with an interquartile range from 35.0 to 193.0. For standard tablets, the median is 141.0 PRU, with an interquartile range from 8.0 to 197.0. These summaries describe the central value and the middle portion of the observed values in each arm. They do not show the full distribution, and the broad ranges indicate that individual measurements varied within both groups.

A one-hour platelet measure addresses the pharmacodynamic question stated in the registry: whether platelet reactivity differs shortly after the loading dose. It is not itself a clinical event outcome. The record does not report a between-arm estimate with a confidence interval or a primary-endpoint p-value, so the precision and statistical evidence for a comparative effect cannot be assessed from the posted primary summaries alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: A randomized comparison aims to make treatment groups comparable, on average, with respect to factors that may affect outcomes. Randomization supports a causal comparison when allocation is implemented as planned and the analysis preserves the randomized groups. The registry identifies the study as randomized and parallel, but does not describe the sequence-generation or allocation-concealment procedures. It also does not say which participants or staff were masked. The term single masking is recorded, but the masked party is not reported in the registry record.

Why report a median and interquartile range?

General: The median is the middle of the ordered observations, while the interquartile range describes the middle half of the observations. These summaries can be useful when a distribution is skewed or includes values that make a mean and standard deviation less representative of a typical observation. The registry specifies the median and interquartile range for PRU. The posted summaries are 94.0 with an interquartile range of 35.0 to 193.0 for orodispersible tablets, and 141.0 with an interquartile range of 8.0 to 197.0 for standard tablets.

The two arm summaries are descriptive. A difference between medians is not itself a complete inferential comparison. A comparative analysis would ordinarily state the estimand, the method used to compare groups, and an estimate with uncertainty. For a median-based comparison, the method and assumptions matter because the uncertainty of a median is not conveyed by the interquartile range alone. A confidence interval would communicate a range of values compatible with the data under the specified model and procedure. The primary endpoint's comparative estimate, confidence interval, and p-value are not reported in the registry record.

How should binary outcomes be read?

General: For an outcome recorded as whether a participant experienced an event, a risk difference expresses the difference between the proportions in the two groups. A confidence interval communicates uncertainty around that estimate. If the interval includes no difference, the data are compatible with no difference as well as with effects in either direction under the method used. If it excludes no difference, that is evidence against a null difference for that particular unadjusted comparison, but it does not address multiplicity, bias, or clinical importance.

The posted binary-outcome comparisons are unadjusted calculations, not analyses reported by the sponsor. For insufficient antiaggregation, the risk difference is -0.031, with a confidence interval from -0.168 to 0.107 and p = 0.661. For residual platelet reactivity, the risk difference is 0.508, with a confidence interval from 0.364 to 0.651 and p < 0.001. For clinically relevant bleeding events, the risk difference is -0.061, with a confidence interval from -0.12 to -0.003 and p = 0.042. These estimates are not adjusted for other outcomes or covariates. The record lists no reported analyses for these outcomes.

What do the planning illustrations represent?

General: A sample-size calculation estimates the number of participants that would be needed under stated assumptions to detect a specified effect with a chosen error rate and power. It is a planning exercise, not a measure of the probability that a completed trial found a true effect. The record's illustrations are based on observed effects, use a two-sided significance level of 0.05, equal allocation, and a normal approximation. They give participants per arm for 80% and 90% power at 100%, 75%, and 50% of the observed effect. These are not the trial's original design justification, and they should not be described as observed power.

For the insufficient antiaggregation comparison, the planning illustration lists 2,652 and 3,550 participants per arm for 80% and 90% power when planning for 100% of the observed effect; for 75%, it lists 4,647 and 6,221; for 50%, it lists 10,301 and 13,789. For the residual platelet reactivity comparison, the corresponding figures are 14 and 18 for 100%, 23 and 30 for 75%, and 47 and 62 for 50%. These calculations are sensitive to the observed effect used as their starting point. In particular, estimates derived from an observed effect may be unstable and should not be treated as independent evidence that the effect is real or reproducible.

What is and is not reported about analysis?

The registry lists no reported analyses. Consequently, the unadjusted comparisons should not be attributed to the sponsor or treated as the prespecified analysis. The record does not report the statistical test used for the primary endpoint, a primary-endpoint effect estimate, a primary analysis population, covariate adjustment, handling of missing outcomes, or a procedure for controlling type I error across outcomes. It also does not report whether there were interim analyses or stopping rules. Those details cannot be inferred from the posted arm summaries.

General: Over-dispersion occurs when observed variability in count data exceeds what a simple statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. No count-data model is described in the registry record, and there is not enough information to determine whether over-dispersion is relevant to any analysis in this trial. For the primary PRU outcome, the posted median and interquartile range do not supply the individual-level data needed to assess distributional shape or fit a model.

For rare or sparse events, estimates can be imprecise and sensitive to small changes in event counts. A confidence interval and suitable method are important, but the adverse-event summary does not include comparative uncertainty estimates. More generally, statistical significance is not a measure of effect size, clinical importance, or certainty that results will reproduce. Interpretation requires the estimate, its precision, the study design, and the analysis plan; several of those elements are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, but does not report how statistical testing across outcomes was planned. No adjustment for multiple comparisons, testing hierarchy, or distinction between confirmatory and exploratory outcomes is reported in the registry record. This matters because separate unadjusted tests across multiple outcomes can produce nominally small p-values even when no single effect is especially compelling. The posted secondary p-values should therefore be interpreted as unadjusted findings, not as results protected against multiplicity.

Missing-data methods and analysis populations are also not reported. The registry lists 130 participants enrolled and 65 participants per arm in the posted endpoint summaries, but it does not state whether every randomized participant contributed to every outcome, how unavailable measurements were handled, or whether any participants were excluded from an analysis. It does not identify an intention-to-treat, per-protocol, or safety population. The absence of these details limits assessment of attrition and whether the reported groups preserve the randomized comparison.

The record lists no reported analyses, and it does not describe a statistical analysis plan, interim analyses, stopping boundaries, or a sample-size justification for the original study. The planning illustrations attached to observed secondary effects are not evidence of the original design rationale. The primary endpoint lacks a reported comparative estimate and inferential result, making it impossible to judge the primary analysis method or its precision from the registry record. These omissions do not establish that the procedures were absent; they mean the procedures are not reported in the registry record.

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: reinfarction (1.5%).

The registry's adverse-event summaries list serious adverse events among 1 participant in the orodispersible group and 0 participants in the standard-tablet group. Other adverse events are listed for 14 and 15 participants, respectively. Deaths are listed as 0 in both groups. Reinfarction is identified as a serious adverse-event term, with a reported value of 1.5%.

These are descriptive counts. The registry does not report a comparative analysis, confidence interval, or test for the serious-event summaries, and the number of events is too limited to support precise conclusions about relative safety. A count of participants with an event is not the same as a complete account of event timing, severity, causality, or recurrence. Those details are not reported in the registry record.

The separately listed clinically relevant bleeding outcome is a secondary outcome and should not be conflated with the general adverse-event summary. Safety results should be understood in the context of the recorded follow-up and the details available in the registry; they do not establish the presence or absence of a safety difference.

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

The posted primary results describe platelet reactivity one hour after a loading dose in the two randomized groups. The median PRU was 94.0 for orodispersible tablets and 141.0 for standard tablets, with interquartile ranges of 35.0 to 193.0 and 8.0 to 197.0. The registry notes that lower PRU levels are associated with the expected antiplatelet effect. These data are descriptive, and the record does not report a primary between-group estimate or its uncertainty.

The trial therefore does not support a complete statistical judgment about the primary comparison from the registry results alone. A comparison of the arm medians without a confidence interval or reported test cannot establish the precision of the apparent difference. The secondary outcomes add context, but their unadjusted analyses, lack of a reported testing plan, and differing patterns mean that they cannot be treated as definitive corroboration or as a substitute for the primary analysis.

The results also do not by themselves establish an effect on clinical outcomes. PRU is a pharmacodynamic measure described in the registry, not a clinical event. The listed adverse events and bleeding outcome provide limited descriptive information, but the record does not report comparative safety analyses with uncertainty. Neither a favorable biological measure nor an isolated secondary p-value should be translated into a claim about clinical benefit or harm.

More complete interpretation would require the planned primary comparison, its effect estimate and confidence interval, analysis population, missing-data approach, and definitions for the secondary outcomes. The registry record does not report these details. The appropriate reading is therefore limited to the posted summaries and unadjusted secondary comparisons, with substantial caution about precision and confirmatory evidence.

13. Why This Trial Matters Statistically

This trial illustrates why an outcome's summary statistic and a between-group analysis answer different questions. The median PRU and interquartile range show the observed central values and spread within each arm. They do not provide the estimate and uncertainty for the contrast that the clinical question asks about. Without that contrast, readers cannot determine how precisely the groups differed on the primary endpoint.

It also shows how secondary outcomes can tell a more complicated story than a single primary measure. The posted secondary comparisons do not all point in the same direction, and no multiplicity plan or sponsor-reported analyses are listed. Recognizing that distinction prevents unadjusted results from being treated as a coherent set of confirmatory tests.

Finally, the planning illustrations demonstrate the dependence of sample-size estimates on the assumed effect. They are based on observed secondary effects and stated planning assumptions, not the original trial justification. Such illustrations can aid future planning, but they do not reveal whether the original study was adequately designed for its primary endpoint. In this record, the original sample-size justification and primary comparative analysis are not reported.

The statistical importance of the record is therefore not only the group summaries, but also what is needed to interpret them: a prespecified analysis, clearly defined outcomes and populations, uncertainty estimates, and a transparent account of multiplicity and missing data. Without those elements, descriptive results remain useful but cannot carry the same inferential weight as a complete, reported primary analysis.

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.

A trial-specific limitation is that the posted primary result consists of arm-level median PRU values and interquartile ranges without a reported between-arm estimate, confidence interval, or p-value. The primary comparison is consequently less interpretable than the descriptive summaries alone might suggest. The record also does not describe the test used to compare the primary outcome or clarify whether the analysis was adjusted.

The secondary outcomes have limited contextual detail. The registry does not give the definition or threshold for insufficient antiaggregation, and it does not report separate counts for each residual platelet-reactivity timepoint. The posted result uses the time frame 2, 4 and 6 hours, but the way the measure is constructed across those times is not explained. The clinically relevant bleeding comparison is based on few events, and no comparative safety uncertainty estimates are reported.

The record does not report the randomization procedure, allocation concealment, identity of the masked party, participant flow, analysis populations, or methods for handling missing data. It also does not report a multiplicity strategy, the original sample-size justification, or interim analysis methods. These details may exist outside the registry record, but they cannot be assessed from the information recorded there.

The trial population is described as patients with STEMI or very high-risk NSTEMI undergoing primary PCI. The record does not provide further eligibility details or demographic characteristics in the listed details. This restricts assessment of how representative the enrolled participants were of other clinical populations. These limitations concern the scope and transparency of the posted evidence; they do not establish that unreported procedures were not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ticagrelor Administered as Standard Tablet or Orodispersible Formulation — NCT03822377.
• Registry record last updated 2021-09-08; status last verified 2021-08.
• Results first posted 2021-09-08.
• 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

NCT03822377 is a completed phase 3 randomized, parallel-group study with single masking, sponsored by Azienda Ospedaliero Universitaria di Sassari. The registry lists enrollment of 130, a start date of 2019-06-27, and a primary completion date of 2020-08-31. Participants with ST elevation myocardial infarction or very high-risk non-ST elevation myocardial infarction undergoing primary PCI received ticagrelor 180 mg as either orodispersible or standard coated tablets.

The primary outcome was VerifyNow PRU one hour after the loading dose. The posted arm summaries are medians and interquartile ranges, but a primary comparative estimate and inferential result are not reported. Three secondary outcomes have posted results, with unadjusted comparisons and no reported analyses. The registry record does not report multiplicity handling, missing-data methods, analysis populations, or the original sample-size justification.