Maintenance of Platelet Inhibition With Cangrelor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maintenance of Platelet Inhibition With Cangrelor (NCT00767507), a randomized phase 2 study. The primary outcome is Stage I: Percentage of Patient Samples That Maintained Platelet Inhibition Levels of Greater Than or Equal to 60% as Reported by the VerifyNow P2Y12 Point of Care Assay..

2. Clinical Question

The clinical setting is a transition between stopping oral platelet-inhibiting treatment and undergoing surgery. The registry’s stated purpose was to assess the safety profile of cangrelor infusion in that period and whether surgery could proceed without excessive peri-operative bleeding. Those stated aims provide context, but they do not turn the primary endpoint into a direct measure of surgical safety: the primary endpoint is platelet reactivity, expressed as the percentage of samples meeting a specified inhibition threshold.

The posted primary results concern two Stage I cangrelor cohorts, while the posted Stage II outcomes include cangrelor and placebo arms. The registry record does not report a Stage II primary-endpoint comparison. Consequently, the primary endpoint results and the Stage II safety outcomes address related but distinct questions, and should not be treated as if they were a single randomized comparison.

3. Trial Design

The registry classifies the study as phase 2, randomized, triple-masked, and parallel-group, with enrollment of 221. The condition listed is acute coronary syndrome, and the study status is completed. The registry lists The Medicines Company as sponsor. The start is recorded as 2008-10 and primary completion as 2011-06.

The record describes two stages. Stage I included a cohort receiving cangrelor at 0.5 mcg/kg/min and a cohort receiving cangrelor at 0.75 mcg/kg/min. Their posted primary endpoint results are percentages of samples meeting the platelet-inhibition threshold. Stage II included a cangrelor arm at 0.75 mcg/kg/min and a placebo arm; the posted Stage II outcomes include CABG-related bleeding and blood-product transfusions. The registry record does not report the detailed allocation process between stages or cohorts.

The cangrelor and placebo regimens are described as continuous intravenous infusions administered for a minimum of 48 hours and a maximum of 7 days. The placebo regimen is described as intended to maintain the blind. The record identifies the overall study as triple-masked, but the specific roles masked, and the practical masking procedures, are not reported in the registry record.

Enrollment is an overall study figure, while the endpoint entries have their own analysis denominators. Those denominators differ across endpoint entries and stages; they should be read alongside the outcome to which each applies rather than assumed to represent a single common analysis population. The registry record does not report further participant-flow details, reasons for any differences in denominators, or detailed definitions of the analysis populations.

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: Stage I was an open-label, dose-finding stage to identify the dose of cangrelor that achieved a level of antiplatelet effect after discontinuation of oral P2Y12 therapy equivalent to the previous oral P2Y12 maintenance therapy. These patients were not enrolled in Stage II. Stage II was randomized, double-blind, placebo-controlled.

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.

Population: This is the Safety Population: Includs both Stage I and Stage II patients who received any study drug and were classified according to the actual treatment received. Stage I (open-label) patients were analyzed based on the dose they received; Stage II (randomized) patients were analyzed based on the actual treatment, cangrelor or placebo, received.

6. Primary Endpoint

The registry lists the primary outcome as Stage I: Percentage of Patient Samples That Maintained Platelet Inhibition Levels of Greater Than or Equal to 60% as Reported by the VerifyNow P2Y12 Point of Care Assay., measured over During study drug infusion up to 1-6 hours prior to surgery.

The primary endpoint is the percentage of patient samples that maintained platelet inhibition of at least 60%, measured with the VerifyNow P2Y12 point-of-care assay during study-drug infusion and up to 1–6 hours before surgery. The record says the threshold was selected as an approximation of the antiplatelet effect expected if oral P2Y12 inhibitors had not been discontinued. It is therefore a laboratory measure tied to a stated pharmacologic target, not a direct count of patients who experienced a clinical event.

The distinction between samples and patients matters. The endpoint is reported as a percentage of samples, so the posted percentages should not automatically be interpreted as percentages of participants. The primary results list 76.5 for the Stage I cohort receiving 0.5 mcg/kg/min, with 5 participants, and 94.4 for the Stage I cohort receiving 0.75 mcg/kg/min, with 6 participants. These are small cohorts, and the registry record does not report confidence intervals or a formal inferential comparison for these primary results.

As a general statistical point, a threshold-based endpoint compresses a continuous laboratory measurement into whether a sample meets a cutoff. That can make a target easier to describe, but the percentage does not show how far individual measurements were above or below the threshold. Nor does it, by itself, establish how the laboratory measure relates to bleeding or other clinical outcomes. The registry’s stated rationale explains why the threshold was chosen; it does not establish that the threshold predicts those outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the trial as randomized, triple-masked, and parallel-group. Random allocation is intended, in general, to make assigned groups comparable on average at the point of assignment. Masking is intended to limit the influence of knowledge about assigned treatment on care, reporting, or assessment. These are general purposes of such design features, not evidence that every source of bias was prevented in this study. Specific procedures for allocation concealment, masking roles, and outcome assessment are not reported in the registry record.

What the endpoint scale means

The primary outcome is a percentage of samples meeting a platelet-inhibition threshold. It is not listed as a conventional participant-level event count or as a mean laboratory value. A percentage based on repeated samples can have a different interpretation from a percentage of participants, because the unit being summarized is the sample. The registry record does not report the number or timing pattern of samples contributed by each participant, or the approach used to account for any within-participant correlation. Without those details, the dependence structure of the sample-level data cannot be assessed from the record.

For the primary endpoint, the posted Stage I values are 76.5 and 94.4, with 5 and 6 participants in the respective cohorts. No confidence intervals, standard errors, or formal comparison are reported for these results. General statistical practice would use an uncertainty estimate to convey how imprecisely a percentage is estimated; without one, the descriptive values should not be treated as highly precise, especially given the small participant counts. The statistical model and handling of repeated samples are not reported in the registry record.

How to read the Stage II comparisons

The Stage II entries for CABG-related bleeding and transfusions are binary outcomes: a participant either has the recorded event or does not. The posted comparisons report risk differences, which express the estimated difference between the event risks in the two arms. A risk difference near zero represents little estimated separation in absolute event risk, while positive and negative values indicate opposite directions under the stated comparison. These are general interpretations of the measure.

Each risk difference is accompanied by a confidence interval and an unadjusted p-value. The confidence interval conveys uncertainty in the estimate; when it spans zero, the data are compatible with a range of possible directions as well as no difference. The p-value is calculated without a reported adjustment for multiple outcomes. It is not a measure of clinical importance, and a large p-value does not demonstrate equivalence. The registry record does not report a prespecified equivalence or non-inferiority margin, so these comparisons cannot be interpreted as demonstrating either form of equivalence.

The risk ratios and odds ratios are also posted for the two Stage II comparisons. As general measures, a risk ratio compares event risks, while an odds ratio compares event odds. Their uncertainty intervals likewise need to be considered alongside the point estimates. They are alternative scales for describing the same binary outcomes, not independent replications of the evidence. The registry record does not report a sponsor analysis for these comparisons; the posted analysis listings are empty, and the displayed recalculations are unadjusted.

Planning illustrations and their limits

The planning illustrations use the observed effect as a starting point and show hypothetical participants per arm for 80% power and for 90% power, across planning for 100%, 75%, and 50% of the observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They are planning illustrations based on the observed effect, not evidence about the trial’s design decisions or its achieved power.

As a general explanation, power is the probability that a specified analysis detects a specified effect under a particular design and set of assumptions. A calculation using an effect observed after the trial is not observed power and cannot establish that the trial had adequate power in advance. Planning counts based on a noisy observed estimate can change substantially if the underlying effect differs from that estimate. The study’s own sample-size rationale, target effect, and design assumptions are not reported in the registry record.

Analysis populations and missing statistical details

The record gives endpoint-specific denominators, but does not report detailed analysis-population definitions, participant flow, missing-outcome handling, or whether all randomized participants were analyzed in their assigned groups. Although one secondary outcome title refers to an ITT population, the registry record does not provide enough detail to determine how that population was defined or how missing observations were treated. The statistical plan, model specifications, covariate adjustments, and any interim analyses are not reported in the registry record. These omissions limit independent assessment of how closely the posted summaries reflect the original analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes and reports unadjusted comparisons for two of them. It does not report whether the analyses were prespecified in a protocol, whether outcomes were organized into a hierarchy, or whether any multiplicity adjustment was planned or applied. When several outcomes are tested, unadjusted p-values do not account for the combined opportunity for chance findings. As a general statistical point, this makes isolated secondary p-values less persuasive as confirmatory evidence, especially when the record does not document a testing strategy.

The primary endpoint has descriptive Stage I values, but a formal inferential analysis is not reported. The registry record also does not report interim analyses or stopping rules. Their absence from the record cannot establish whether they were or were not part of the original study conduct; the relevant details are not reported in the registry record.

Details about missing data are also not reported in the registry record. It does not describe the amount or reasons for missing endpoint data, methods for handling missing observations, or sensitivity analyses. The posted outcome denominators vary by endpoint and stage, but the record does not explain the participant flow behind those denominators. The entry for platelet reactivity refers to an ITT population in a secondary outcome title, but the registry record does not provide a full definition of the analysis population or explain how it was formed.

These reporting gaps matter because statistical conclusions depend on who was included, how incomplete measurements were handled, and how multiple outcomes were interpreted. Without the protocol, statistical analysis plan, or fuller analysis descriptions in the registry record, it is not possible to verify which comparisons were confirmatory, how missingness was addressed, or whether the reported analyses followed a prespecified plan.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiogenic shock (3.8%), cardiac arrest (2.8%), cardiac failure (2.0%), respiratory failure (1.9%), atrial fibrillation (1.0%).

The adverse-event record gives serious-event and other-event counts separately for the Stage I cohorts and Stage II arms. In Stage II, serious adverse events are recorded for 11 of 106 participants in the cangrelor arm and 9 of 101 in the placebo arm. Other adverse events are recorded for 27 of 106 and 23 of 101, respectively. Stage I counts are based on the much smaller cohorts, so those entries are descriptive and do not support precise comparisons.

These figures are counts of participants with recorded events, not measures of whether an event was caused by the assigned infusion. Seriousness is a classification of an event, not proof of treatment causation. The record also lists serious-event terms with percentages, including cardiogenic shock and cardiac arrest; it does not provide enough detail in these entries to interpret those percentages as comparative risks between arms.

Deaths are recorded as null for the adverse-event groups. That means a death count is not available in these entries; it should not be interpreted as a count of zero. The registry record does not report further detail about event timing, attribution, recurrence, or statistical comparisons of adverse events. The counts therefore describe the posted safety record but do not, on their own, establish a causal safety difference.

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

The results describe a small Stage I laboratory endpoint and several Stage II clinical outcomes in a phase 2 study. The primary results are percentages of samples meeting the platelet-inhibition threshold, rather than a direct clinical outcome comparison. The Stage II entries offer randomized-arm comparisons for bleeding and transfusions, but their estimates have wide confidence intervals that include no difference and extend in both directions.

These findings do not establish that cangrelor and placebo are equivalent on the reported clinical outcomes. Failure to show a clear difference is not the same as demonstrating equivalence; that would require an appropriate design, a prespecified margin, and an analysis suited to that question. Such a margin and analysis are not reported in the registry record. Nor do the posted results establish that cangrelor causes a specific difference in the reported outcomes.

The primary endpoint’s rationale is to approximate a stated platelet-inhibition target during the preoperative period. Meeting that target is not itself evidence of a particular clinical outcome. The registry record does not report an analysis connecting the platelet-reactivity endpoint with bleeding, transfusions, or other clinical events. Interpretation should therefore keep the laboratory result separate from the clinical-event comparisons.

The uncertainty is substantial: the primary Stage I cohorts have few participants, and the Stage II comparisons do not precisely determine the direction or size of an effect. The registry record also lacks details about missing data, analysis populations, multiplicity handling, and the statistical analysis plan. These limitations do not erase the posted observations, but they restrict how strongly those observations can support broader conclusions.

In practical statistical terms, the record is most informative as a description of the measured outcomes and their uncertainty, not as a definitive test of clinical benefit, harm, or equivalence. It does not justify a treatment recommendation. The trial’s stated purpose and the posted results should be distinguished: an aim to evaluate safety is not itself evidence that safety was established.

13. Why This Trial Matters Statistically

This trial illustrates why endpoint type and study stage matter when reading clinical results. The primary endpoint is a laboratory measurement summarized as the percentage of samples meeting a threshold, while the posted Stage II outcomes are participant-level clinical events. These measures answer related but nonidentical questions. A favorable-looking result on a laboratory endpoint cannot be substituted for evidence about a clinical event, and a clinical event comparison does not explain the underlying laboratory response without a reported linkage analysis.

It also shows why the analysis denominator and unit of observation deserve attention. The primary endpoint refers to samples, but the result entries include participant counts. Without details about sample collection and repeated measurements, a reader cannot fully assess how those samples contribute to the percentages or how their dependence was handled. This is a general issue for studies in which multiple measurements may come from each participant.

The Stage II comparisons provide a further teaching point about uncertainty. A point estimate alone can suggest a direction, but the confidence interval indicates how much uncertainty remains. Here the intervals include no difference and permit effects in either direction. That is not proof of no effect, and it is not proof of equivalence. A precise clinical conclusion requires more than a nonsignificant p-value.

Finally, the registry record demonstrates the importance of statistical reporting. Analysis-population definitions, missing-data methods, multiplicity plans, and the original sample-size rationale are not reported. Without these details, readers cannot fully evaluate whether the analyses answer prespecified questions or how robust the results are to analytic choices. Clear reporting of these elements is essential for interpreting a trial independently and for distinguishing descriptive findings from confirmatory evidence.

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.

Several limitations are specific to the available record. The primary endpoint results are from Stage I cohorts with 5 and 6 participants, and no uncertainty intervals or formal comparison are reported for those percentages. The primary outcome is measured in samples, but the number of samples per participant and the handling of repeated measurements are not reported in the registry record. This makes it difficult to judge the precision and statistical structure of the primary summaries.

The Stage II clinical outcomes are secondary, and the registry record does not report a multiplicity strategy. The reported comparisons are unadjusted recalculations from posted counts; no sponsor-reported analyses are listed. Their confidence intervals are broad and include no difference, so the comparisons leave substantial uncertainty about both direction and magnitude. The registry record does not report an equivalence or non-inferiority framework.

Further limitations include the lack of detailed participant flow, outcome-specific missing-data information, analysis-population definitions, and statistical model specifications. The registry record does not report the study’s sample-size justification, interim-analysis procedures, or complete statistical analysis plan. Although the record classifies the study as randomized and triple-masked, the allocation procedures and roles masked are not reported in the registry record.

The adverse-event entries are counts, with deaths recorded as null, and do not supply event attribution or comparative analyses. These reporting limitations mean that event counts should be read descriptively rather than as proof of causation. Taken together, the record permits a cautious reading of the posted summaries but does not permit a full audit of the planned and performed statistical analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Maintenance of Platelet Inhibition With Cangrelor — NCT00767507.
• Registry record last updated 2014-04-04; status last verified 2014-02.
• Results first posted 2014-04-04.
• 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

The registry record describes NCT00767507, “Maintenance of Platelet Inhibition With Cangrelor,” as a completed phase 2, randomized, triple-masked, parallel-group study with enrollment of 221. It lists acute coronary syndrome as the condition and The Medicines Company as sponsor. The recorded study start is 2008-10, and primary completion is 2011-06.

The primary endpoint is the percentage of samples meeting a platelet-inhibition threshold of at least 60% during infusion before surgery. The posted Stage I results are 76.5 for the 0.5 mcg/kg/min cohort and 94.4 for the 0.75 mcg/kg/min cohort. Stage II includes cangrelor and placebo arms, with posted secondary outcomes for CABG-related bleeding and blood-product transfusions.

The Stage II estimates are imprecise, and the registry record does not report formal analyses for these outcomes, a multiplicity strategy, detailed missing-data methods, or the full statistical analysis plan. The results are therefore best read as descriptive and uncertain rather than definitive evidence of a clinical difference or equivalence.