Clinical Management of Argatroban in Patients With Heparin Induced Thrombocytopenia Type II: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Management of Argatroban in Patients With Heparin Induced Thrombocytopenia Type II (NCT00861692), a na phase 2 study. The primary outcome is Composite of All-cause Death, Thrombosis (New and Extended) and Unplanned Amputation.

2. Clinical Question

In statistical terms, the record describes an observational account of outcomes in a treated group, not an experiment that estimates a contrast between assigned groups. The absence of a comparator matters because outcomes during treatment cannot, by themselves, show what would have happened to the same population under another management strategy. The record also does not report how suspected and confirmed cases were distinguished for analysis, or whether the primary composite was assessed in all enrolled participants. Those details would help define the population to which any outcome description applies.

3. Trial Design

This is a Phase 2, open-label, multicentre clinical study listed as single-group. The registry reports enrollment of 20 participants, no masking, and allocation marked NA. Argatroban is the listed intervention, and the study status is completed. The sponsor is Tanabe Pharma Corporation. The study start is recorded as 2009-04 and primary completion as 2011-02.

These design labels describe the structure of the study, not the magnitude or certainty of its results. Single-group means the record does not describe a separate control group for a concurrent comparison. Open-label means masking is listed as none. Multicentre indicates that the study was conducted across more than one centre, but the number and identity of centres are not reported in the registry record. Other operational details, including the treatment regimen, recruitment process, follow-up procedures, and site-specific procedures, are not reported in the registry record.

The registry’s stated purpose was to collect information on argatroban clinical management in patients with suspected or confirmed heparin-induced thrombocytopenia Type II who required parenteral antithrombotic therapy, with or without ongoing thrombosis. The design can describe events recorded among participants receiving the intervention, subject to the completeness and definitions of the collected data. It cannot establish a randomized treatment contrast because no randomized allocation or comparator is described.

Completed status indicates the registry lists the study as completed; it does not mean that every planned outcome or analysis is publicly reported. The record lists seven outcome measures and zero analysis records. The primary outcome result, analysis population, and statistical methods used for outcome estimation are not reported in the registry record. No sample-size justification or prespecified statistical analysis plan is reported there either.

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 Composite of All-cause Death, Thrombosis (New and Extended) and Unplanned Amputation, measured over During and 30 days after argatroban treatment.

The primary endpoint is a composite of all-cause death, new or extended thrombosis, and unplanned amputation. Its unit is participants, and its timeframe is during argatroban treatment and 30 days after treatment. The registry identifies the component events but does not report their definitions, the method for confirming them, or the primary endpoint result.

General statistical rationale: a composite endpoint combines multiple outcomes into a single measure. This can capture several clinically important types of event and provide one overall outcome for analysis. Interpretation depends on the components: a combined result does not reveal which component occurred, how often each occurred, or whether the components carry similar importance. Component-level results are therefore useful alongside the composite when available.

For a binary composite, the central descriptive quantity is typically the number or proportion of participants experiencing at least one component during the specified period. In this record, the outcome parameter is listed as a number of participants, but no result count or proportion is reported. A confidence interval would communicate the precision of an estimated event frequency, but no such interval is reported in the registry record. Without the endpoint count and its analysis details, the outcome cannot be quantitatively interpreted from this record.

The composite is not a comparison of argatroban with another treatment. Even if an event count were available, a single-group count would describe observed participants rather than identify the effect attributable to treatment. The registry record also does not report whether each component was analyzed separately.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a binary primary outcome, expressed as the number of participants with a composite event. It does not report the observed primary outcome count, an effect estimate, a confidence interval, a p-value, or a statistical analysis description. The concepts below are general explanations of methods that may be relevant to binary outcomes; they are not claims about analyses performed in this study.

What does a binary outcome count represent?

A binary outcome classifies each participant according to whether the defined event occurred during the specified observation period. For this study, the composite event includes all-cause death, new or extended thrombosis, and unplanned amputation. A participant with one or more components would ordinarily be counted as having experienced the composite, but the registry does not report its operational definition or how overlapping components were handled. It also does not report whether the outcome was assessed for every enrolled participant.

A count can be informative as a description of observed participants. A proportion can place that count in relation to the number assessed, while an interval estimate can convey the uncertainty around an estimated event frequency. These quantities answer different questions: the count describes events, the proportion describes frequency in the analyzed group, and the interval characterizes precision under a specified statistical method. None of the primary outcome values or intervals is reported in the registry record.

What would a confidence interval tell a reader?

General explanation: a confidence interval gives a range of values compatible with the data under the assumptions of the method used. A narrow interval indicates greater statistical precision than a wide interval, but it does not resolve limitations such as selection, measurement error, or lack of a comparator. It is not a guarantee that the true value lies in the interval, nor does it state the probability that a particular treatment effect is true. Since the primary outcome estimate and interval are not reported, the precision of the study’s primary result cannot be described.

Why does the single-group design matter?

General explanation: an intervention effect is a contrast between outcomes under different treatment conditions. A single-group study observes participants under one described condition and does not directly provide the alternative outcome needed for that contrast. Comparing an observed event frequency with a historical or external value would require additional information and assumptions; no such comparison is reported in the registry record. The absence of randomization also means the record cannot use randomized allocation to balance prognostic factors between treatment groups.

Open-label design means masking is listed as none. General explanation: when treatment and assessment are unmasked, knowledge of treatment may influence care decisions, reporting, or outcome assessment, depending on the outcome and procedures. The registry does not describe assessment safeguards or the extent to which outcome ascertainment was standardized. This is a possible design consideration, not proof that bias occurred.

How should a composite endpoint be assessed?

General explanation: combining components can create a broad endpoint, but the aggregate result can conceal differences among components. The frequency of the composite does not identify which event drove it. Component-specific counts and definitions help readers understand the clinical and statistical meaning of a composite. Those component results are not reported for the primary endpoint in this registry record.

What do the planning assumptions mean?

The record describes planning illustrations based on a stated fraction of an observed effect. The assumptions list a two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The illustrations are planning calculations, not observed outcomes or evidence of the study’s achieved power. The record is single-group and does not describe a randomized two-arm comparison, so those assumptions do not describe its trial design. No numerical planning results are reported in the registry information available for this analysis.

General explanation: a sample-size calculation depends on the target effect, variability or event frequency, significance threshold, desired power, allocation, and statistical model. Changing assumptions can change the planning estimate. Calculations built from an observed effect are especially conditional: the observed effect may be imprecise, and a planning illustration does not establish that the original study had a particular probability of detecting an effect. No protocol sample-size justification or original design calculation is reported in the registry record.

What analyses are documented?

The registry lists zero analysis records. It does not report the analysis population, a model for the primary endpoint, a confidence-interval method, or a missing-data procedure. These absences should not be filled by assuming a standard approach. A registry outcome title and its measurement timeframe identify the intended topic, but do not specify how data were analyzed or how uncertainty was quantified.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Argatroban")
n      <- c(20)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Argatroban  20  10  50.0  27.2  72.8  29.9  70.1  29.8  70.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and zero analysis records. It does not report a statistical analysis plan, identify which outcomes were formally tested, or describe an adjustment for multiple comparisons. It is therefore not possible to determine whether multiplicity was addressed, whether a testing hierarchy was prespecified, or how the primary outcome related to any other analyses. These details are not reported in the registry record.

General statistical explanation: when multiple outcomes or repeated statistical tests are considered, the chance of at least one apparently notable result can increase if each test is interpreted independently. Methods such as a prespecified hierarchy or adjustment can address that issue, but the appropriate approach depends on the analysis objectives and design. No particular approach should be attributed to this study without a registry description.

The primary outcome result itself is not reported, and no confidence interval or p-value is listed. The record also does not report participant-level analysis populations, such as whether all enrolled participants were included in each outcome assessment. The enrollment figure is 20, but the number assessed for the primary endpoint is not reported in the registry record. It is not possible to establish from the posted information whether participants withdrew, lacked outcome data, or were excluded from any analysis.

Missing-data methods are not reported. General explanation: missing outcome information can affect an estimate if participants with missing data differ systematically from those with observed data. Complete-case analysis, imputation, and sensitivity analysis make different assumptions; none can be inferred. The record also does not state how deaths, treatment discontinuation, or incomplete follow-up were handled for the composite endpoint.

Because the analysis plan and primary results are not reported, the evidence available does not allow readers to assess prespecification, selective reporting, or the robustness of findings to alternative analysis choices. These are reporting limitations, not findings that establish that a particular analysis was omitted or conducted improperly.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (15.0%), peritonitis (10.0%), acute respiratory distress syndrome (10.0%), disseminated intravascular coagulation (5.0%), thrombocytopenia (5.0%).

In the argatroban group, serious adverse events affected 14 of 20 participants, and other adverse events affected 17 of 20. The registry lists sepsis (15.0%), peritonitis (10.0%), acute respiratory distress syndrome (10.0%), disseminated intravascular coagulation (5.0%), thrombocytopenia (5.0%), and acute coronary syndrome (5.0%) among the serious adverse-event terms.

These are event-reporting figures, not estimates of treatment causation. The record does not explain how seriousness was defined, how events were collected, or whether the listed terms are exhaustive. The percentages are reported as recorded; they should not be converted into event counts without additional information. A participant may experience more than one event, so the serious and other adverse-event participant counts should not be added together to infer a total number of distinct participants. The record does not report a death count in this safety group information.

General statistical explanation: adverse-event frequency describes what was recorded in the observed group. Without a comparison group and additional information about underlying illness, concurrent care, and event assessment, such a frequency does not isolate the contribution of a treatment. The registry does not report enough detail to evaluate those factors or to compare safety between treatment strategies.

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

The record establishes that a completed, open-label, single-group Phase 2 study enrolled 20 participants and evaluated argatroban in patients with suspected or confirmed heparin-induced thrombocytopenia Type II requiring parenteral antithrombotic therapy. It also identifies the composite primary outcome and reports adverse-event participant counts and selected serious adverse-event terms. These details describe the study’s setting and some reported safety information.

The record does not report the primary composite outcome result. It therefore does not show the number of participants who experienced all-cause death, new or extended thrombosis, or unplanned amputation during treatment and 30 days after treatment. Nor does it report a confidence interval, p-value, or component-specific primary outcome results. A conclusion about the frequency or precision of that endpoint cannot be drawn from the posted results.

The single-group design does not provide a concurrent treatment contrast. General statistical explanation: outcomes observed in a treated group cannot alone establish what would have occurred under another treatment strategy. This distinction applies even when outcomes are carefully counted; a causal treatment effect requires a suitable comparison and assumptions that the study design can support. No randomized comparison is reported.

The adverse-event counts show that serious and other adverse events were recorded among participants in the argatroban group. They do not show that argatroban caused those events, and they do not establish a comparative safety profile. The record does not provide a death count for this safety listing or enough information to interpret event ascertainment, follow-up completeness, or the relationship between the listed terms and individual participants.

Thus, the information supports a description of the study design and the safety events reported in the registry. It does not support a quantitative interpretation of the primary endpoint or a comparative claim about treatment effects. Additional outcome results, analysis details, and a suitable comparator would be needed to address those questions.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between documenting a clinical study and reporting evidence that can answer a comparative question. The registry gives the intervention, population, design labels, enrollment, primary endpoint, and safety counts. Those elements help readers understand what was studied and what outcomes were intended to be collected.

The single-group design is central to interpretation. A record of events among people who received argatroban can describe that group, but it cannot directly estimate a difference against another strategy. Statistical language should preserve that distinction: observed outcomes are not equivalent to treatment effects. This remains true regardless of whether a study is complete or whether event counts are presented.

The primary endpoint also illustrates why a composite needs component-level context. Combining death, thrombosis, and amputation into one outcome can create a broad summary, but the aggregate count alone would not show which component occurred. In this record, even the composite result is not reported, so neither its overall frequency nor its component pattern can be assessed.

The safety reporting provides another useful distinction: event occurrence and treatment attribution are separate questions. Counts and listed terms describe reports in the intervention group. Without a comparator and relevant assessment details, they do not identify how much of the observed event burden is attributable to the intervention.

Finally, the registry lists no analysis records. This highlights why outcome definitions, analysis populations, handling of missing observations, and precision estimates matter to interpretation. Their absence does not establish that no analyses were performed outside the registry, but it does limit what readers can conclude from this record. Statistical reporting is most useful when design and outcome descriptions are accompanied by estimates, uncertainty, and transparent methods.

15. 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 main limitation for interpreting the primary outcome is that its result is not reported in the registry record. The endpoint is defined by its title and timeframe, but a participant count, estimate of event frequency, interval estimate, and component-specific results are not provided. The registry also leaves the endpoint description and population fields blank, so operational definitions and the analysis population cannot be determined from the record.

The study is listed as single-group, with allocation marked NA and no masking. No concurrent comparator is described. Therefore, the design does not provide a direct randomized contrast, and observed events cannot be interpreted as comparative treatment effects. Open-label conduct may be relevant to outcome reporting or assessment in general, but the registry does not describe how events were assessed or whether any safeguards were used.

Enrollment is 20, but the number of participants with evaluable primary outcome data is not reported. The record does not describe withdrawals, loss to follow-up, missing-data handling, or exclusions from analysis. It also does not report whether the primary composite was analyzed as one endpoint only or alongside component outcomes.

Further details not reported in the registry record include eligibility criteria, participant characteristics, argatroban regimen, treatment duration, centre count, outcome adjudication procedures, sample-size justification, interim analyses, and a statistical analysis plan. The record lists seven outcome measures and zero analysis records, but does not explain the selection or analysis of those outcomes. These gaps limit evaluation of precision, completeness, prespecification, and generalizability.

The safety listing reports participant counts and selected serious-event terms, but does not provide event-level detail, attribution, or a death count. The safety information should therefore be read as descriptive reporting in this group, not as a causal or comparative assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Management of Argatroban in Patients With Heparin Induced Thrombocytopenia Type II — NCT00861692.
• Registry record last updated 2026-01-06; status last verified 2025-12.
• Results first posted 2015-12-22.
• 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.

19. Record Summary

NCT00861692 is a completed Phase 2, open-label, multicentre, single-group study sponsored by Tanabe Pharma Corporation. It enrolled 20 participants and evaluated argatroban in patients with suspected or confirmed heparin-induced thrombocytopenia Type II who required parenteral antithrombotic therapy, with or without ongoing thrombosis. The recorded study start is 2009-04 and primary completion is 2011-02.

The primary endpoint is a composite of all-cause death, new or extended thrombosis, and unplanned amputation during treatment and 30 days after treatment. Its result is not reported in the registry record. The argatroban group safety listing reports serious adverse events in 14 of 20 participants and other adverse events in 17 of 20. The record lists seven outcome measures and zero analysis records; statistical methods, missing-data handling, and a comparative analysis are not reported.