This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Antithrombotic Effects of Ticagrelor Versus Clopidogrel (NCT01642238), a randomized phase 4 study. The primary outcome is Platelet-thrombus Formation in an ex Vivo Model of Thrombosis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01642238 |
| Phase | Phase 4 |
| Condition | Acute Coronary Syndrome |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Juan J Badimon |
| Results posted | Yes |
2. Clinical Question
Population
The registry lists acute coronary syndrome as the condition and enrollment of 15. Further participant characteristics, eligibility details, and the population included in the primary analysis are not reported in the registry record. The result therefore describes the posted study population without allowing a detailed assessment of how closely it represents any particular clinical group.
Intervention
The intervention was a single loading dose of ticagrelor, given with aspirin and bivalirudin. The registry describes ticagrelor as 180 mg, given as two 90 mg tablets; aspirin as one 81 mg tablet; and bivalirudin as a 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg/hour for 1 hour.
Comparator
The comparison was a single loading dose of clopidogrel, also given with aspirin and bivalirudin. Clopidogrel was described as 600 mg, given as two 300 mg tablets. The aspirin and bivalirudin regimens were the same as those listed for the ticagrelor treatment.
Primary question
The study asked whether platelet-thrombus formation in an ex vivo model changed from pretreatment baseline to 1 hour with the ticagrelor combination, and how that posted result compared with the clopidogrel combination. The endpoint is a percent change in thrombus size; a positive change represents a decrease in size. The registry record does not report an inferential test of the difference between treatments.
3. Trial Design
The registry describes this as a randomized, crossover study with no masking. The treatments were ticagrelor plus aspirin plus bivalirudin and clopidogrel plus aspirin plus bivalirudin. Enrollment was 15, and the record is marked completed. The listed study period runs from 2012-07 to primary completion in 2013-03. It is identified as phase 4.
In a crossover design, participants receive more than one treatment in a sequence, so treatment comparisons may use within-participant information. This differs from a parallel-group design, in which each participant receives only one assigned treatment. The registry lists two sequences in the safety information: ticagrelor, then clopidogrel; and clopidogrel, then ticagrelor. However, details such as the randomization procedure, treatment-period timing, washout arrangements, and handling of period or sequence effects are not reported in the registry record.
The posted primary endpoint summaries give n: 15 for each treatment. Those arm-specific counts should not be read as evidence of two separate parallel groups in a crossover study. The record does not explain the participant flow or how many observations contributed to each endpoint estimate. It also does not report a named primary-analysis population or a statistical model accounting for the crossover structure.
The study’s stated purpose was to compare the antithrombotic effects of the treatment combinations. The primary endpoint concerns platelet-thrombus formation in an ex vivo model, while the record also lists platelet reactivity and blood thrombogenicity among secondary outcomes. These measures address laboratory or model-based outcomes; the registry record does not describe a clinical-event endpoint as the primary outcome.
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.
First Intervention (1 Day)
| Stage | Ticagrelor, Then Clopidogrel | Clopidogrel, Then Ticagrelor |
|---|---|---|
| STARTED | 7 | 8 |
| COMPLETED | 7 | 8 |
| NOT COMPLETED | 0 | 0 |
Washout (1-2 Weeks)
| Stage | Ticagrelor, Then Clopidogrel | Clopidogrel, Then Ticagrelor |
|---|---|---|
| STARTED | 7 | 8 |
| COMPLETED | 7 | 8 |
| NOT COMPLETED | 0 | 0 |
Second Intervention (1 Day)
| Stage | Ticagrelor, Then Clopidogrel | Clopidogrel, Then Ticagrelor |
|---|---|---|
| STARTED | 7 | 8 |
| COMPLETED | 7 | 8 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Antithrombotic Effects |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | years | 31.2 (26.8 to 35.6) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 9 |
| Body mass index | kg/m^2 | 27.0 (24.9 to 29.1) |
6. Primary Endpoint
The registry lists the primary outcome as Platelet-thrombus Formation in an ex Vivo Model of Thrombosis, measured over Pre-treatment baseline and 1 hour.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is platelet-thrombus formation in an ex vivo model of thrombosis. It is reported as the mean percent change in thrombus size at 1 hour compared with pretreatment baseline. In the registry’s definition, a positive change means a decrease in thrombus size. This direction is important when reading the values: the sign describes change in the measured model outcome, not a treatment effect estimate comparing the two regimens.
An ex vivo thrombosis model provides a controlled way to measure blood-related activity outside the body. Such measurements can be useful for studying biological responses to different treatment combinations. They are not, by themselves, direct measures of clinical outcomes such as events experienced by patients. The registry record does not report validation details for the model, the measurement procedure, or how the endpoint was assessed.
The timeframe is pretreatment baseline and 1 hour. The reported estimates are means with 95% confidence intervals for each treatment. A confidence interval expresses uncertainty around an estimate under the statistical method used; it is not a range containing every participant’s result. The registry does not provide a comparative confidence interval for the treatment difference or identify the method used to calculate the posted intervals.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted mean percent change was 56.3 for ticagrelor plus aspirin plus bivalirudin, with a 95% confidence interval from 43.5 to 69.0. For clopidogrel plus aspirin plus bivalirudin, the posted mean was 35.2, with a 95% confidence interval from 23.9 to 46.5. Under the endpoint definition, positive values represent decreases in thrombus size relative to pretreatment baseline. These are treatment-specific summaries, not a direct estimate of the difference between treatments.
The intervals convey uncertainty around each arm’s mean estimate. Their widths indicate that the estimates are not exact, and the interval endpoints should be considered when describing precision. They do not show the spread of individual participant values, because the record reports confidence intervals rather than a standard deviation or another measure of participant-level variability. The method used to obtain these intervals is not reported in the registry record.
Because this is a crossover study, a treatment comparison would ordinarily need to reflect the paired nature of observations when the same participants receive treatments in sequence. The record does not report a treatment contrast, its confidence interval, a p-value, or an analysis model. It is therefore not possible to determine from these summaries alone how uncertain the difference between the treatment conditions is, or whether an analysis accounted for the crossover design.
The registry lists 0 analyses. That absence matters: the arm-specific means and intervals do not substitute for an explicit between-treatment analysis. In particular, comparing whether separate confidence intervals overlap is not a formal test of a treatment contrast. No new contrast should be calculated from the posted summaries, and the descriptive results should not be presented as a statistical conclusion about which regimen has the larger effect.
The endpoint is a laboratory-model measure, and the posted primary result does not establish what the observed changes mean for clinical outcomes. The registry record also does not report a statistical analysis plan, missing-data approach, or information about the participants contributing to each estimate. These gaps limit interpretation of both precision and generalizability. The result is best read as a pair of descriptive mean changes, with the stated confidence intervals, in the registered ex vivo endpoint.
9. Statistical Methods Explained
What does a mean describe?
A mean is a summary of the observed values in a group or treatment condition. For a continuous endpoint such as percent change in thrombus size, it provides a central estimate on the endpoint’s measurement scale. A mean does not show how similar or different individual measurements were. That requires a measure of variability or participant-level data, neither of which is reported beyond the confidence intervals for the means.
The posted means are 56.3 for ticagrelor plus aspirin plus bivalirudin and 35.2 for clopidogrel plus aspirin plus bivalirudin. The endpoint definition assigns a particular direction to positive values: they represent a decrease in thrombus size. The values should be read in that stated direction, while keeping in mind that they summarize change from baseline within each treatment condition. They are not themselves a between-treatment effect estimate.
What does a 95% confidence interval communicate?
A confidence interval communicates the uncertainty associated with an estimate under a specified statistical procedure. In repeated use of a procedure under its assumptions, intervals constructed in that way would cover the target parameter at the stated rate. For an individual interval, it is not correct to say that there is a 95% probability that the fixed parameter lies between its endpoints. Nor does an interval describe where most participant values fall.
The registry reports a 95% confidence interval of 43.5 to 69.0 for the ticagrelor combination and 23.9 to 46.5 for the clopidogrel combination. Their endpoints help readers see the uncertainty around each mean. The record does not name the calculation method, so the assumptions behind the intervals cannot be checked from the posted information. A confidence interval for each treatment mean is also different from a confidence interval for the treatment contrast.
Why does the crossover design matter?
General statistical explanation: when each participant receives multiple treatments, measurements from that participant may be related. A paired analysis can use those within-participant comparisons and account for the fact that observations from the same person are not independent. Crossover analyses may also need to consider treatment period or sequence, depending on the design and the analysis plan.
The registry calls this a randomized crossover study and lists the two treatment sequences in its safety information. It does not report the model or test used for the primary outcome, whether the comparison was paired, or whether period and sequence were considered. The posted n of 15 for each treatment does not establish how the data were analyzed or whether the same participants contributed to both treatment summaries. Without those details, the suitability of a particular analysis cannot be assessed.
Why is a treatment contrast needed?
The scientific question compares treatment conditions. A suitable inferential result would ordinarily describe the estimated contrast, its uncertainty, and the method used to evaluate it. The record gives only arm-specific means and confidence intervals, and lists 0 analyses. It does not report a contrast estimate, a p-value, or a comparative confidence interval. It is not appropriate to create a contrast by subtracting the posted means, because that would be a new calculation and would not account for the crossover design or its uncertainty.
General statistical explanation: an inferential comparison depends on more than the two point estimates. It also depends on the variability of the measurements and, in a crossover, potentially on within-participant association and design features. A descriptive difference between two means cannot reveal the uncertainty of the treatment comparison on its own. Separate intervals do not resolve that question.
What is over-dispersion, and is it relevant?
General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. It is especially relevant for count outcomes, where a simple model may underestimate variability if the data are more heterogeneous than expected. This primary endpoint is continuous and reported as a mean, so the registry record does not establish that over-dispersion is a concern for this outcome. More broadly, checking whether a model’s assumptions fit the data requires details that are not reported.
The posted result is therefore interpretable as a descriptive summary with stated intervals, but not as a complete inferential comparison. The analysis method, assumptions, and model diagnostics are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures and identifies 6 secondary outcomes, including platelet reactivity and blood thrombogenicity. The record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical plan specifying how multiple outcomes or comparisons would be interpreted. When many outcomes are examined, the chance of a nominally unusual result can increase; general statistical practice may address this through prespecified priorities or adjustment methods. Which approach, if any, was used in this study is not reported in the registry record.
The registry lists 0 analyses. It therefore does not provide analysis-level results for the secondary outcomes in the information. Their presence in the outcome list should not be confused with posted inferential findings. The record also does not identify a primary-analysis population, describe exclusions, or explain how missing measurements were handled. The population field for the primary endpoint is blank.
For a crossover study, completeness across treatment periods can affect which within-participant comparisons are available. The registry does not report whether any endpoint measurements were missing, whether participants contributed data in both periods, or whether an imputation or other missing-data procedure was used. These omissions prevent an assessment of whether the reported estimates reflect all randomized participants or a subset with available measurements.
Any planning calculations based on the observed effect are illustrations rather than observed power. The record describes such calculations as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the detectable effect specified as a fraction of the observed effect. The registry record does not report the calculation outputs here, and these planning assumptions are not evidence of the trial’s original design rationale.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ticagrelor, Then Clopidogrel | 0 | 15 | 0.0% |
| Clopidogrel, Then Ticagrelor | 0 | 15 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ticagrelor, Then Clopidogrel | 0 of 15 |
| Clopidogrel, Then Ticagrelor | 0 of 15 |
The registry reports two treatment-sequence groups: ticagrelor, then clopidogrel, and clopidogrel, then ticagrelor. For each sequence, 15 participants are listed as at risk for serious adverse events, and 0 as affected. The other adverse-event figures also list 15 at risk and 0 affected in each sequence. Deaths are recorded as null, which means a death count is not reported in the registry record; it should not be interpreted as a reported zero.
These are descriptive safety counts in a small crossover study, not proof that adverse events cannot occur. A count of 0 affected means none were recorded in the posted category for that group, but the record does not provide event definitions, collection procedures, follow-up duration, or a detailed safety analysis. The sequence groups should not automatically be treated as independent treatment groups, because the study is described as crossover. No serious adverse-event terms are listed. The figures can be reported as posted, while recognizing that they provide limited information about safety beyond the recorded observation.
12. What the Result Does, and Does Not, Mean
The result describes mean change in an ex vivo platelet-thrombus measure at 1 hour compared with pretreatment baseline. The posted mean is 56.3, with a 95% confidence interval from 43.5 to 69.0, for ticagrelor plus aspirin plus bivalirudin. The corresponding mean is 35.2, with a 95% confidence interval from 23.9 to 46.5, for clopidogrel plus aspirin plus bivalirudin. Positive values are defined as decreases in thrombus size.
These results do not, on their own, quantify the treatment contrast. The registry does not report a comparative estimate, comparative confidence interval, p-value, or analysis method. Since the design is crossover, a valid treatment comparison would need to reflect the design and the relationship between measurements from the same participants. The posted arm summaries are not enough to reconstruct that analysis.
The endpoint also does not directly measure a clinical event. It is a laboratory-model outcome, so its meaning is limited to the measured ex vivo response unless further evidence connects it to outcomes that matter to patients. The record does not report such a connection or clinical outcome results for this primary endpoint. Accordingly, the posted change should not be treated as evidence that either treatment is clinically superior or inferior.
The record leaves important interpretive details unspecified, including the analysis population, missing-data handling, and the method used to calculate the confidence intervals. The outcome list includes secondary measures, but no analyses are listed. Taken together, the available information supports a narrow description of the two treatment-specific estimates and their stated uncertainty, not a definitive conclusion about comparative effectiveness or clinical benefit.
13. Why This Trial Matters Statistically
This trial illustrates why design and analysis details matter as much as the reported point estimates. In a crossover study, each participant may contribute information under multiple treatments, making the within-participant structure central to the comparison. Arm-specific summaries alone do not show whether that structure was used in the analysis. A treatment contrast and its uncertainty are needed to address the comparative question directly.
It also demonstrates the distinction between a model-based biological outcome and a clinical outcome. Platelet-thrombus formation in an ex vivo model can provide a defined measure of antithrombotic activity under the study conditions. But a change in that measure is not equivalent to a change in a patient-level clinical outcome. Keeping that distinction clear prevents a laboratory result from being given a broader interpretation than the registry supports.
The study record gives confidence intervals for the mean changes, which communicate uncertainty around those estimates, but not around a treatment contrast. It lists 0 analyses and does not provide a statistical model, missing-data approach, or named analysis population. Those omissions make the result a useful example of how descriptive outcome reporting can be informative while still leaving the principal comparative inference unresolved.
Finally, the posted safety counts show how to distinguish a recorded zero from an unreported value: affected counts are 0, whereas deaths are null. That distinction is essential when reading registry results. The study therefore matters statistically as a case for careful interpretation of crossover summaries, uncertainty, endpoint scope, and incomplete analysis reporting.
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 registry record does not provide a comparative treatment estimate or its uncertainty, despite the study’s comparative question. It lists 0 analyses and does not identify the statistical method used for the primary endpoint. As a result, the posted arm-specific means and confidence intervals cannot establish the inferential result of the crossover comparison.
Details needed to evaluate the crossover analysis are not reported, including the timing of treatment periods, washout arrangements, treatment sequence procedures, and handling of period or sequence effects. The two sequence labels appear in the adverse-event information, but the primary outcome summary does not explain how sequence was incorporated. It also does not clarify whether the n of 15 shown for each treatment represents complete paired observations.
The record does not report participant characteristics beyond the listed condition, a primary-analysis population, endpoint-level missingness, or a missing-data method. It does not describe the ex vivo measurement procedure or the derivation of the confidence intervals. Further, the primary outcome is a model-based measure rather than a reported clinical event, and no link between the measured change and clinical outcomes is described.
Multiplicity handling for the 8 outcome measures is not reported. The registry also does not provide a statistical analysis plan or an explanation of the planned sample size. These limitations do not invalidate the descriptive summaries, but they constrain conclusions about precision, the comparative effect, and the broader relevance of the endpoint.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Antithrombotic Effects of Ticagrelor Versus Clopidogrel — NCT01642238.
- Registry record last updated 2016-07-11; status last verified 2016-06.
- Results first posted 2016-07-11.
- 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.
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18. Record Summary
The registry describes a completed phase 4 randomized crossover study, with no masking, comparing ticagrelor plus aspirin plus bivalirudin with clopidogrel plus aspirin plus bivalirudin. Enrollment was 15. The primary endpoint was mean percent change in platelet-thrombus size in an ex vivo model at 1 hour versus pretreatment baseline; positive change represents a decrease in thrombus size.
The posted mean was 56.3 (95% confidence interval, 43.5 to 69.0) for the ticagrelor combination and 35.2 (95% confidence interval, 23.9 to 46.5) for the clopidogrel combination. The registry lists 0 analyses and does not report a treatment contrast or the method used for the primary analysis. Missing-data handling and the primary-analysis population are also not reported in the registry record. The findings are therefore descriptive treatment-specific summaries, not a complete comparative inference.