Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI) (NCT00508924), a randomized phase 2 study. The primary outcome is Activated Clotting Time (ACT) Value After the First Dosing of Study Treatment..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, open-label, parallel-group, multicentre phase II study. It was marked completed and records enrollment of 140. The stated setting was elective PCI. Patients were treated with clopidogrel and aspirin alongside one of the anticoagulant regimens: argatroban labelled ARG250, ARG300 or ARG350, or unfractionated heparin.

Randomization is intended to assign treatment by chance, which can reduce systematic differences between groups at baseline. It does not guarantee that groups will be identical, particularly in a study of this size, and the posted record does not provide baseline characteristics or details of the randomization procedure. The allocation ratio and any stratification factors are not reported in the registry record.

The study was open-label, meaning masking was not used. Knowledge of assigned treatment can affect care, reporting, or outcome assessment, depending on the outcome. ACT is a laboratory measure, but the registry record does not describe how samples were collected, whether assessment was blinded, or how measurement procedures were standardized across centres.

The stated objective was to examine dose-response in pharmacodynamic markers and assess anticoagulation, safety and efficacy relative to heparin, with dual antiplatelet therapy. The posted primary result concerns ACT shortly after the initial bolus. The registry record lists 2 outcome measures and no secondary outcomes posted. It does not report a protocol, detailed statistical plan, follow-up schedule beyond the primary endpoint timeframe, or a justification for the enrollment target. The trial start is recorded as 2005-08; a completion date is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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 Activated Clotting Time (ACT) Value After the First Dosing of Study Treatment., measured over 5 - 10 min after initial bolus.

Activated clotting time (ACT) is a measure of how long blood takes to clot under a standardized testing procedure. In this trial it was recorded in seconds 5 - 10 min after the initial bolus of study treatment. ACT is used as a pharmacodynamic marker: it can describe the anticoagulant effect detected soon after treatment is given. It is not, by itself, a direct measure of a clinical event such as myocardial infarction or bleeding.

The registry record specifies a median and an inter-quartile range (IQR) for this endpoint. The median describes the middle of the observed values when they are ordered. The IQR describes the central spread of the values, from the first quartile to the third quartile. The posted summaries give the median and the IQR limits for each arm. These summaries convey both the location and spread of ACT values without assuming that the values follow a symmetric distribution.

Timing is important to interpretation: the result pertains to the stated interval after an initial bolus, not to ACT at every point during PCI or during later follow-up. The registry record does not explain whether the endpoint was measured once per participant, how repeated measurements were handled, or whether measurements outside the stated interval were allowed. It also does not report a target ACT range or a prespecified threshold for interpreting an individual value.

As a general statistical point, a pharmacodynamic marker can help characterize treatment response, but a difference in a marker does not by itself establish a difference in clinical outcomes or safety. The posted ACT summaries should therefore be read as measurements of clotting time at the specified assessment, rather than as a complete account of the clinical effects of the regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record posts group-level summaries rather than participant-level data or a fitted statistical model. For the primary endpoint, it gives the median ACT and IQR limits for each randomized arm, together with the number of participants represented in each group. No inferential analysis is listed. The interpretation is therefore descriptive: it concerns the values recorded in the arms and does not estimate a formal between-group effect with uncertainty.

Why report a median and IQR?

As a general statistical explanation, the median is the midpoint of an ordered set of observations. It is less influenced by extreme values than the arithmetic mean. The IQR spans the central half of the observations and gives a sense of their spread. A median and IQR can be informative when a measurement has a skewed distribution or when extreme observations are possible. They do not reveal the shape of the entire distribution, and group summaries cannot show how individual values overlap or how paired or repeated measurements behave.

The registry record identifies the dispersion as an inter-quartile range and provides lower and upper limits for each arm. Those limits should be read as the reported spread around the median, not as a confidence interval for the median or for a treatment difference. A confidence interval, in general, expresses uncertainty about an estimated quantity under a statistical procedure. No confidence interval for the primary endpoint comparison is reported.

What does randomization contribute?

In general, random assignment helps prevent treatment choice from being systematically linked to participant characteristics. It supports a causal comparison when allocation, follow-up, measurement and analysis are handled appropriately. Randomization does not ensure balance in every characteristic, and the registry record does not provide baseline summaries or enough procedural detail to assess how randomization was implemented. The record also does not identify an analysis population, such as all randomized participants or only participants with an endpoint measurement.

The parallel-group structure means that participants were assigned to one treatment arm rather than being described as receiving each treatment in sequence. The record does not report crossover, treatment switching, or adherence information. Those features should not be inferred from the design label alone.

What can be inferred from the ACT summaries?

The medians and IQRs describe the observed ACT distributions by arm at the specified assessment time. A formal comparison could, in general, estimate a difference between groups or use a model suited to the endpoint and design. The registry record does not say whether any such test or model was used, and it reports no analysis results. It is not appropriate to reconstruct a p-value or confidence interval from the medians and IQR limits alone: those summaries do not contain enough information about the observations or the analysis procedure.

The study objective includes examining dose-response. In general, dose-response analysis examines whether outcomes vary systematically with treatment dose or ordered dose groups. A visual or numerical ordering of arm medians can be a descriptive clue, but it does not account for within-arm variability or establish a trend. The treatment labels are ARG250, ARG300 and ARG350; the units and fuller dose descriptions are not reported in the registry record. No trend estimate or dose-response test is reported.

How should planning calculations be read?

In general, sample-size planning calculations ask how many participants might be needed to detect a specified effect under stated assumptions. Such calculations are not observed trial outcomes and are not evidence that a trial had a particular probability of detecting an effect after it was conducted. The registry record describes planning assumptions based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It does not report the trial's own design justification. Planning illustrations should not be mistaken for a prespecified analysis, an observed effect, or observed power.

The posted data structure identifies this study as not reduced to one comparison and indicates that values are missing or not estimable for a two-arm comparison for another endpoint. Thus, a single pairwise effect is not available from the posted results for that endpoint. The registry record does not report recalculated comparisons that could resolve this issue. Any recalculated result would be an unadjusted calculation from posted summary statistics and would not supersede a sponsor analysis if a discrepancy were identified; no discrepancy is indicated in this record.

What uncertainty remains?

Summary measures do not show individual-level variation, the presence of outliers, or the distribution's shape. Without a reported statistical analysis, the precision of arm-to-arm differences is unknown. The registry record also does not describe missing-data methods, covariate adjustment, handling of multiple outcomes, or sensitivity analyses. These absences limit both reproducibility and the strength of interpretation. They do not establish that an analysis was not performed elsewhere; they mean that it is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures, no secondary outcomes posted and no analyses. It does not provide a statistical analysis plan or state which outcomes were included in any formal hypothesis-testing strategy. The record therefore does not explain whether the primary endpoint was the only confirmatory test, whether several comparisons were planned, or whether any adjustment for multiple testing was used.

Multiplicity matters in general when researchers test several outcomes, time points or treatment contrasts. As the number of tests grows, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The posted record does not give enough information to determine whether multiplicity arose or how it was handled. No p-values are reported for the primary endpoint, so no claim about a multiplicity-adjusted or unadjusted statistical result can be made.

Missing-data details are also not reported in the registry record. The ACT summaries are based on 36 participants in ARG250, 38 in ARG300, 31 in ARG350 and 33 in the heparin arm. The record does not explain whether participants without an ACT measurement were excluded, whether measurements were unavailable for another reason, or whether any imputation was performed. It does not state whether the reported counts represent all randomized participants or a subset with endpoint data.

The analysis population is not described. The registry record does not say whether analyses followed randomized assignment regardless of treatment received, or whether participants were analyzed according to treatment received or another rule. Interim analyses, stopping rules, covariate adjustment and sensitivity analyses are not reported in the registry record. These gaps prevent a complete assessment of how the results were selected and analyzed; they do not show that a particular method was or was not used outside the registry record.

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: coronary artery dissection (3.1%), myocardial infarction (3.1%), abdominal pain upper (3.1%), catheter site haemorrhage (3.1%), chest pain (3.1%).

The safety results report serious adverse events and other adverse events by group. Serious adverse events were recorded for 4 of 36 participants in ARG250, 5 of 38 in ARG300, 7 of 32 in ARG350 and 4 of 34 in the heparin group. Other adverse events were recorded for 22 of 36, 25 of 38, 23 of 32 and 27 of 34 participants, respectively. These are the reported event counts and at-risk group sizes; they are not adjusted comparisons.

The registry record lists serious-event terms including coronary artery dissection, myocardial infarction, upper abdominal pain, catheter site haemorrhage, chest pain and basilar migraine, each with a listed value of 3.1%. The record does not associate these terms with particular treatment arms in the displayed information, so they should not be attributed to a specific group. The death counts are not reported in the registry record.

Safety counts require attention to their denominators and definitions. The at-risk counts are not identical to the ACT endpoint counts in every arm, and the registry record does not explain the difference. The listed figures do not establish that events were caused by a treatment, nor do raw counts account for exposure duration, event severity beyond the serious classification, or differences in participant characteristics. The registry record does not report a formal comparative safety analysis or uncertainty estimates. These figures describe recorded events and should not be treated as a test of whether the regimens differ in safety.

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

The posted primary results describe ACT values 5 - 10 min after the initial bolus in four treatment arms. The median values are 301.0 for ARG250, 330.0 for ARG300, 354.0 for ARG350 and 237.5 for heparin, with arm-specific IQR limits reported. These figures show the observed ordering of the group medians at that assessment. They do not, on their own, provide a formal estimate of a treatment contrast or its precision.

The record does not report statistical tests, confidence intervals, adjusted analyses or a dose-response estimate for ACT. It therefore does not establish whether observed differences are compatible with chance variation under a specified statistical model, nor how precisely any group difference is estimated. The summaries also do not establish whether an ACT difference is clinically important. The registry record does not state a threshold for clinical interpretation.

ACT is a pharmacodynamic marker, not a complete clinical outcome. These data do not by themselves determine whether one anticoagulant regimen changes the risk of a clinical event or has a favorable overall balance of benefits and harms. The adverse-event counts are descriptive, without reported comparative uncertainty or attribution of individual serious-event terms to arms. The registry record does not report death counts.

The study is described as phase II and concerns elective PCI with clopidogrel and aspirin. Findings from this setting should not automatically be generalized to other clinical settings, populations or treatment combinations. Eligibility criteria and further population details are not reported in the registry record. The study's stated aim includes safety and efficacy assessment, but the posted information supports only the outcomes and summaries actually recorded.

In general, statistical interpretation separates what was measured from what can be concluded about a broader population or treatment effect. Here, the record supports a description of the arm-level ACT distributions and adverse-event counts. It does not support a definitive claim that a particular regimen is better, worse, or equivalent to another, and it does not provide evidence about outcomes that are not reported.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between descriptive results and comparative evidence. The registry record gives group medians and IQR limits for a pharmacodynamic endpoint, which allow readers to see the central ACT values and their within-group spread. But the absence of reported inferential analyses means those summaries cannot answer how precisely the treatment groups differ or whether a prespecified statistical criterion was met.

The design also makes the limits of a dose-response claim visible. Three argatroban arms have ordered labels, and their reported medians are ordered, but a trend in group summaries is not equivalent to a dose-response analysis. Such an analysis would need a clearly specified treatment scale, statistical method and uncertainty estimate. The registry record does not report those details, and the dose units are not reported.

The open-label design and the endpoint's timing matter to interpretation. ACT was recorded shortly after an initial bolus, so the result addresses a defined pharmacodynamic moment rather than all phases of care or later clinical outcomes. General statistical principles distinguish a measurable biological response from patient-relevant outcomes; results on one do not automatically determine results on the other.

Finally, the safety figures illustrate why counts need context. Group-specific at-risk sizes are reported, but the record does not provide a comparative safety model, event attribution, or death counts. Readers can identify the recorded counts, but cannot use them alone to rank the regimens reliably. The value of the registry record is therefore in making the available summaries and reporting gaps explicit, rather than in establishing a definitive comparative conclusion.

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 features of the registry record limit interpretation. It gives no formal statistical analysis for the primary ACT endpoint, no p-values or confidence intervals for treatment contrasts, and no adjusted estimates. The reported medians and IQRs are useful descriptions but do not permit reconstruction of a valid comparison or its precision from the available summaries.

The record describes the study as randomized and open-label, but does not report the allocation ratio, randomization procedure, baseline characteristics or blinding of endpoint assessment. It also does not provide detailed eligibility criteria, a description of the analysis population, treatment adherence information, or a detailed account of measurement procedures. The arm descriptions are empty, and dosing units are not reported; the ARG250, ARG300 and ARG350 labels should therefore be treated as labels rather than full regimen descriptions.

The primary endpoint concerns ACT 5 - 10 min after the initial bolus. The registry record does not describe later ACT measurements or provide detailed clinical outcome results beyond the listed outcome information. It lists 2 outcome measures but no secondary outcomes posted and no analyses. A statistical plan, multiplicity approach, missing-data procedures, interim analyses and sensitivity analyses are not reported in the registry record.

The ACT endpoint counts and safety at-risk counts differ in some arms, without an explanation of the populations represented. Serious adverse-event terms are listed with percentages but are not assigned to treatment arms in the posted information. Death counts are not reported in the registry record. These omissions limit interpretation of both the endpoint summaries and the safety profile. The record's limitations concern what can be assessed from registry reporting; they do not establish what analyses or procedures may have occurred outside that record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI) — NCT00508924.
• Registry record last updated 2026-01-06; status last verified 2025-12.
• Results first posted 2012-12-05.
• 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

NCT00508924 is a completed randomized, open-label, parallel-group, multicentre phase II study of anticoagulation in patients undergoing elective PCI. The record describes argatroban in three arms labelled ARG250, ARG300 and ARG350, compared with unfractionated heparin, alongside clopidogrel and aspirin. Enrollment is recorded as 140.

The primary endpoint is ACT in seconds 5 - 10 min after the initial bolus. The record posts arm-level medians and IQR limits, with endpoint counts of 36, 38, 31 and 33 for ARG250, ARG300, ARG350 and heparin, respectively. It also posts serious and other adverse-event counts by group. No inferential analyses are listed, and the record does not report a statistical analysis plan, missing-data methods, analysis populations or comparative uncertainty estimates.

The results support a descriptive account of the recorded ACT values and adverse events. They do not establish a statistically precise or clinically definitive comparison among the regimens.