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 Trial to Assess the Ocular Safety of Vorapaxar (SCH 530348) in Participants With Atherosclerosis (Study P05183) (NCT00617123), a randomized phase 3 study. The primary outcome is Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00617123 |
| Phase | Phase 3 |
| Condition | Atherosclerosis, Ischemia, Myocardial Infarction |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 258 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
The clinical question concerns whether participants assigned to vorapaxar had a different occurrence of a specified retinal finding from participants assigned to placebo during follow-up. The finding was vacuolization in the inner nuclear layer of the retina, assessed using ocular coherence tomography (OCT). It was defined by a change from baseline: more than one vacuole, with a vacuole described as a clear, round structure in the retinal inner nuclear layer at least 30 microns in diameter, in either eye.
Population
Participants with established atherosclerotic disease enrolled in the TRA 2°P - TIMI 50 Study (P04737). For the primary-outcome analysis, the registry describes participants who took at least one dose of study medication and had a baseline and at least one post-baseline vacuolation assessment.
Intervention
Vorapaxar 2.5 mg, administered orally once daily for 1 year.
Comparator
A matching placebo tablet administered orally once daily for 1 year.
Primary question
How many participants developed the defined OCT finding during follow-up of up to 12 months, and how did that occurrence compare between the randomized groups?
The registry frames the study as an evaluation of long-term ocular safety in participants already enrolled in the parent study. The primary endpoint is a participant count, rather than a measure of average retinal thickness or an average imaging score. The record also lists visual acuity and additional OCT and fundus photography outcomes. Those measures describe other aspects of ocular status; they do not replace the specified primary question.
The registry record does not report a primary-outcome comparison, its uncertainty, or group-specific primary endpoint counts. Therefore, the clinical question is identifiable from the protocol description, but the posted record does not show an estimate that answers it.
3. Trial Design
This was a randomized, double-blind, placebo-controlled, parallel-group Phase 3 study. The registry records triple masking. Enrollment was 258, and the study status is completed. The study is titled as an assessment of vorapaxar’s ocular safety in participants with atherosclerosis and is linked to participants in the TRA 2°P - TIMI 50 Study (P04737).
Participants were assigned to vorapaxar 2.5 mg or matching placebo. The arm descriptions specify oral administration once daily for 1 year. The primary endpoint was assessed over a timeframe of up to 12 months. The registry lists a study start date of 2008-07-01 and a primary completion date of 2010-10-01. These dates describe the study record and do not establish how long any individual participant was observed.
Randomization is intended, in general, to make treatment groups comparable at assignment with respect to both measured and unmeasured characteristics. Blinding is intended, in general, to reduce the influence of treatment knowledge on participants, clinical care, and outcome assessment. The registry identifies randomization and triple masking, but does not describe the procedures used to generate or conceal assignments, or who was masked in detail. Those details are not reported in the registry record.
The registry lists a total enrollment of 258, but it does not provide group-specific enrollment counts in the information describing the primary endpoint. The analysis population was defined more narrowly: participants had to take at least one dose and have both a baseline and at least one post-baseline vacuolation assessment. The number meeting those criteria is not reported in the registry record. Thus, the enrollment count should not be treated as the denominator for the primary endpoint.
The intervention schedule and primary assessment timeframe are described, but the registry record does not report the visit schedule, timing of individual OCT assessments, treatment adherence, or follow-up completeness. It also does not report a sample-size justification or details of how the study’s ocular safety objective informed its design.
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: A total of 258 particpants were referred to opthalmology sites, 65 of whom did not particpate in this study (P05138) beyond the screening visit and were not included in the analysis of ocular safety. A total of 193 participants were included in the analysis of ocular safety.
Referral Screening Period
| Stage | Vorapaxar | Placebo |
|---|---|---|
| STARTED | 137 | 121 |
| COMPLETED | 98 | 95 |
| NOT COMPLETED | 39 | 26 |
Reasons for not completing this period:
| Reason | Vorapaxar | Placebo |
|---|---|---|
| Did Not Meet Protocol Eligibility | 36 | 24 |
| Did Not Wish To Continue | 3 | 1 |
| Adverse Event | 0 | 1 |
Study Treatment Period
| Stage | Vorapaxar | Placebo |
|---|---|---|
| STARTED | 98 | 95 |
| Treated | 97 | 95 |
| COMPLETED | 81 | 79 |
| NOT COMPLETED | 17 | 16 |
Reasons for not completing this period:
| Reason | Vorapaxar | Placebo |
|---|---|---|
| Withdrawal by Subject | 8 | 12 |
| Adverse Event | 7 | 3 |
| Did Not Meet Protocol Eligibility | 2 | 0 |
| Noncompliance with Protocol | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis population consisted of all participants who took at least one dose of study medication, and had a baseline and at least one post-baseline vacuolation assessment.
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: Participants who were included in the analysis of ocular safety.
| Characteristic | Unit | Vorapaxar | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 98 | 95 | 193 | |
| Age, Continuous | years | 56.6 (SD 10.1) | 55.3 (SD 11.7) | 55.9 (SD 10.9) |
| Sex: Female, Male: Female | Participants | 27 | 26 | 53 |
| Sex: Female, Male: Male | Participants | 71 | 69 | 140 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Who Develop Vacuolization in the Inner Nuclear Layer (INL) of the Retina as Measured by Ocular Coherence Tomography (OCT), measured over Up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who develop vacuolization in the inner nuclear layer of the retina, as assessed by OCT. The registry defines the finding relative to baseline: more than one vacuole in either the left or right eye, with each vacuole defined as a clear, round structure in the inner nuclear layer at least 30 microns in diameter. The stated assessment period is up to 12 months.
This endpoint converts an imaging finding into a participant-level event. In general, a defined event threshold can make an outcome easier to interpret as the number of people meeting a prespecified criterion. The threshold also determines what the count means: it is not a count of all visible structures, a continuous measure of retinal change, or a measure of visual function. A participant meeting the definition in either eye is within the endpoint’s stated scope.
OCT is the specified assessment method for this retinal structural outcome. The registry also lists visual acuity, center foveal thickness measured by OCT, numerical scores of abnormalities measured by OCT, and numerical scores of abnormalities measured by fundus photography as secondary outcomes. These outcomes address distinct features and should not be treated as interchangeable with the primary endpoint.
The registry provides the endpoint definition and analysis-population criteria, but does not report the group-specific counts or a comparison. It therefore does not show how often the endpoint occurred or how precisely any difference between groups was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of vorapaxar and placebo, but does not report a primary-outcome result that permits a statistical comparison. The primary endpoint is described as a participant count, and the analysis population is defined, yet group-specific event counts, an effect estimate, a confidence interval, and a p-value are not reported in the registry record. Without those quantities, the size and direction of any observed difference cannot be assessed from this record.
The outcome measure is identified as the number of participants who develop retinal vacuolization by OCT. The registry’s analysis listing does not include an analysis for this endpoint; the record also flags that the primary outcome has several categories or time points and was not reduced to one comparison. Accordingly, a single primary comparison should not be inferred from the outcome description. A listed endpoint is not itself evidence that an event occurred, nor does the absence of a posted comparison establish that the groups were the same.
Precision cannot be evaluated without an estimate and its uncertainty. In general, a confidence interval describes a range of values compatible with the data and the chosen method; its width helps convey how precisely an effect has been estimated. No such interval for the primary comparison is reported in the registry record. It is therefore not possible to distinguish a tightly estimated small difference from an imprecisely estimated difference using this record alone.
The study reports enrollment of 258, but the endpoint analysis population required at least one dose and both baseline and post-baseline assessment. The number included in that analysis is not reported in the registry record. The enrollment total cannot substitute for the endpoint-specific denominator, and it does not reveal how many participants contributed outcome data in each group.
The record lists secondary ocular outcomes, but does not report their results in the information describing the study. Nor does the record describe the handling of multiple outcomes or assessment times. Without those details and the relevant estimates, the secondary measures cannot be used to fill the gap in the primary comparison.
These limitations concern what can be concluded from the registry record, not what the study may have found in other records. The registry documents a completed trial and a planned ocular safety assessment, but the posted information does not quantify the primary endpoint’s occurrence or the comparative uncertainty. No conclusion about the direction, magnitude, or statistical significance of a treatment-group difference is supported by the reported primary-outcome information.
9. Statistical Methods Explained
The design is a randomized, double-blind, placebo-controlled, parallel-group study. In general, random assignment supports a comparison by limiting systematic differences between groups at the point of assignment. A parallel design follows distinct groups assigned to different treatments. Blinding is intended to limit the influence of treatment knowledge on behavior, care, and outcome assessment. The registry identifies triple masking, but does not give operational details of the allocation or masking procedures; those details are not reported in the registry record.
What kind of outcome is this?
The primary endpoint is expressed as the number of participants who develop a defined event. For a participant, the endpoint can be understood as meeting or not meeting the stated OCT criterion during the specified assessment period. The reported endpoint is therefore a count of people meeting the definition, not a continuous average measure. In general, an analysis of a binary event may compare event proportions, estimate a difference or ratio between groups, or model the event probability. Which method was used for this study is not reported in the registry record.
The definition has several operational parts: the finding is assessed by OCT, concerns the inner nuclear layer, is defined relative to baseline, requires more than one vacuole, and applies to either eye. The registry defines a vacuole as a clear, round structure at least 30 microns in diameter. In general, clear operational criteria help make an endpoint reproducible, while also determining which findings qualify as events. The registry record does not report further details about image reading, adjudication, or quality control.
What does randomization contribute?
Randomization creates the basis for comparing treatment groups without relying solely on observed baseline characteristics to account for differences. In general, chance imbalances can still occur, especially when outcome events are limited. The registry does not report baseline comparisons, the randomization sequence, allocation concealment, or an adjusted analysis for the primary endpoint. Consequently, the record does not establish whether the primary comparison was adjusted or unadjusted, or what covariates may have been considered.
Blinding can matter for an imaging endpoint because knowledge of treatment assignment could influence assessment or decisions about whether a finding meets a criterion. That is a general methodological consideration, not a claim about how images were read in this study. The registry states triple masking but does not identify the masked roles or give details of image assessment. Such information is not reported in the registry record.
How should uncertainty be understood?
In general, an effect estimate describes the observed comparison between groups, while a confidence interval conveys uncertainty around that estimate. A p-value, when used, summarizes how compatible the observed data are with a specified null hypothesis under the chosen statistical model. Neither measure can be interpreted without knowing the estimate, analysis population, and method. The registry record does not report a primary comparison, confidence interval, or p-value, so no claim about statistical significance or precision can be made from the posted primary outcome.
For event counts, the observed number of events and the number of participants assessed in each group are important context. The total enrollment does not give those denominators. The endpoint population excludes participants without the required baseline and post-baseline assessment, and its group-specific size is not reported in the registry record. In general, differing amounts of missing outcome information can affect both the precision and interpretation of a comparison.
What can be inferred about sample-size planning?
The registry record does not report the trial’s sample-size justification, target effect, assumed event frequency, or statistical power calculation. The presence of an enrollment total alone does not show how the study was planned or whether it was sized to detect a particular difference. Any planning illustration based on an observed effect is distinct from the trial’s original design rationale; it is not evidence of observed power and cannot replace a reported estimate with uncertainty.
The record includes a general planning description that uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are assumptions for a planning illustration, not a documented description of the analysis used for the primary endpoint. The record does not report a primary observed effect from which a primary-outcome illustration could be interpreted, and no specific primary comparison is reported.
Why might the analysis method matter?
In general, a statistical model should reflect the outcome structure and the study question. For participant-level event data, a model may account for baseline factors or other design features, but the choice depends on the prespecified analysis plan and available data. Over-dispersion is a general concern when observed variability exceeds what a model assumes; if relevant, it can make standard errors too small unless the method accounts for it. The registry record does not report a model, an over-dispersion assessment, or a method for repeated assessments. No particular modeling approach should therefore be attributed to this study.
Because the primary outcome is described over a follow-up period of up to 12 months, the timing and completeness of assessments could affect the interpretation. The registry does not report an analysis that accounts for differing observation time, nor does it describe whether the endpoint was analyzed at a particular visit or across assessments. The endpoint’s assessment schedule and analysis method are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary ocular endpoint and several secondary ocular outcomes, including visual acuity, center foveal thickness measured by OCT, and numerical abnormality scores from OCT and fundus photography. The registry also notes that the primary outcome has several categories or time points and was not reduced to one comparison. This means that the record does not present a single primary comparison suitable for interpreting as the sole test of the main endpoint.
In general, examining multiple outcomes or time points can increase the chance of at least one apparently notable finding when each is assessed separately. Prespecified hierarchy, adjustment procedures, or other multiplicity strategies can help clarify how such findings should be interpreted. The registry record does not report a multiplicity plan, a testing hierarchy, or an adjustment for multiple comparisons. Those procedures are not reported in the registry record, and no adjustment should be assumed.
The stated primary-outcome analysis population consisted of participants who took at least one dose of study medication and had a baseline and at least one post-baseline vacuolation assessment. This is the population definition in the registry. The record does not report how many participants met it, how participants without assessments were handled, or whether other analysis populations were used.
Missing data can matter when participants with available measurements differ from those without them. In general, complete-case analyses, imputation, and sensitivity analyses make different assumptions about unavailable outcomes. The registry record does not report a missing-data method, reasons for unavailable assessments, or sensitivity analyses. It also does not report whether participants who discontinued treatment continued to have ocular assessments.
Without the analysis population counts, missing-data approach, and multiplicity plan, interpretation must remain limited to the stated endpoint definition and eligibility criteria. The posted information does not show how these issues affected any treatment-group comparison.
11. What the Result Does, and Does Not, Mean
The registry record establishes that an ocular safety study was conducted with randomized assignment to vorapaxar or matching placebo, and that retinal vacuolization assessed by OCT was the primary endpoint. It also defines the participant-level event and the population intended for the primary-outcome analysis. These details explain what the study was designed to assess; they do not provide the comparative result.
The record does not report group-specific primary endpoint counts or a single primary comparison. It therefore does not show whether the defined finding was more or less frequent in either group, how large any difference was, or how uncertain an estimate might be. A completed study status does not by itself supply an outcome result. Likewise, the stated enrollment of 258 is not a count of participants with the endpoint or an endpoint-specific denominator.
In general, a nonsignificant statistical test would not establish that groups are equivalent, and an imprecise estimate could be compatible with a range of effects. Here, the registry does not report the estimate, uncertainty interval, or test needed to make even that distinction. No conclusion about equivalence, absence of an effect, or the direction of a difference follows from the missing comparison.
The endpoint is a defined structural imaging finding, not a direct measure of all aspects of vision or ocular health. The registry lists visual acuity and other imaging outcomes separately, reinforcing that they represent different measures. The primary endpoint definition alone does not establish how a finding relates to participants’ experience or to outcomes beyond the study’s stated follow-up.
The study’s aim is described as evaluating long-term ocular safety in participants with established atherosclerotic disease who were enrolled in a parent study. The specified regimen lasted 1 year, and the primary endpoint timeframe was up to 12 months. The record does not establish what might occur beyond that timeframe or in populations outside the study setting.
The appropriate reading is therefore descriptive: the record documents a randomized ocular safety study and a specific OCT-based endpoint, but does not report the primary comparative result. Any interpretation of benefit, harm, or no difference would require outcome data and analysis details not reported in the registry record.
12. Why This Trial Matters Statistically
This study raises a useful statistical issue: an endpoint can be carefully defined while its comparative result remains unavailable in the registry record. The primary outcome specifies an imaging method, anatomical location, change from baseline, threshold for counting a vacuole, and participant-level event. Such detail supports clarity about what was intended to be measured. It cannot substitute for the observed counts, denominators, and uncertainty needed to interpret a randomized comparison.
The endpoint also illustrates the distinction between an outcome’s measurement scale and its analysis. A finding observed in an eye is summarized as the number of participants meeting the criterion in either eye. In general, moving from eye-level observations to a participant-level outcome requires a clear rule for classifying each participant. The registry gives that rule, but does not report the image-reading procedures or the results that followed from applying it.
The enrollment of 258 is not equivalent to the number analyzed for the primary endpoint. Eligibility for that analysis required study medication exposure and both baseline and post-baseline assessment. The resulting analysis denominator, and any differences in assessment availability between groups, are not reported in the registry record. This distinction matters because estimates and their precision depend on the participants whose outcomes are actually observed.
The record also highlights why registry completeness matters for statistical interpretation. Without a reported primary comparison, readers cannot assess effect direction, magnitude, or precision; without a stated multiplicity approach, they cannot understand how several outcomes and time points were handled. These are not cosmetic reporting details. They determine what claims the posted evidence can support.
For biostatisticians and clinical researchers, the central lesson is to separate design information from results. Randomization, masking, an endpoint definition, and a completed status describe important features of a study, but they do not reveal the estimated treatment contrast. Clear reporting of analysis populations, event counts, methods, and uncertainty is needed to connect design to an interpretable result.
13. 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 endpoint is defined using an imaging threshold and a comparison with baseline. This makes the event dependent on the stated OCT criterion: more than one qualifying vacuole in the inner nuclear layer, in either eye. A participant-level count does not indicate the number of affected eyes or the extent of the imaging finding. The registry does not report eye-level results or additional grading details.
The analysis population requires both a baseline and at least one post-baseline vacuolation assessment, as well as at least one dose of study medication. Participants without those observations are outside the stated primary analysis population. The registry does not report how many participants were excluded by these criteria, why assessments were unavailable, or whether missingness differed between groups. This limits assessment of selection into the analysis and of the completeness of follow-up.
The study is described as assessing long-term ocular safety, but the specified regimen is 1 year and the primary outcome timeframe is up to 12 months. The registry record does not report the distribution of individual follow-up duration or ocular findings after that timeframe. The primary endpoint therefore has a stated time boundary that should be kept in mind when considering the scope of the question.
The study population is described as participants with established atherosclerotic disease enrolled in the TRA 2°P - TIMI 50 Study. That setting defines the population to which the study directly pertains. The registry record does not provide details sufficient to assess how the results might apply outside that parent-study context, and it does not report subgroup-specific primary outcome results.
Finally, the registry does not report the primary endpoint counts, comparison, confidence interval, analysis method, missing-data approach, or multiplicity strategy. These omissions prevent an assessment of the effect estimate and its robustness. The record’s completed status and enrollment total do not resolve those limitations.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Trial to Assess the Ocular Safety of Vorapaxar (SCH 530348) in Participants With Atherosclerosis (Study P05183) — NCT00617123.
- Registry record last updated 2018-09-21; status last verified 2018-08.
- Results first posted 2014-07-14.
- 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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17. Record Summary
The registry describes NCT00617123, a completed Phase 3 randomized, double-blind, placebo-controlled, parallel-group study of vorapaxar 2.5 mg versus matching placebo. Enrollment was 258. Participants were described as having established atherosclerotic disease and being enrolled in the TRA 2°P - TIMI 50 Study. The study regimen was once daily for 1 year, and the primary endpoint timeframe was up to 12 months.
The primary endpoint counted participants who developed a defined OCT finding of vacuolization in the retinal inner nuclear layer relative to baseline. The primary analysis population required at least one dose and baseline and post-baseline assessment. Secondary outcomes included visual acuity and additional OCT and fundus photography measures.
The registry record does not report a single primary-outcome comparison, group-specific event counts, an effect estimate, or its uncertainty. The analysis population size, missing-data handling, statistical analysis method, and multiplicity plan are also not reported in the registry record. Thus, the record describes the study question and design but does not provide the statistical result needed to interpret the primary comparison.