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 Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk. (NCT02740335), a randomized phase 3 study. The primary outcome is Hemostatic Efficacy Rating by IEAB.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02740335 |
| Phase | Phase 3 |
| Condition | Significant Bleeding Risk |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Triple |
| Enrollment | 208 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
Patients receiving vitamin K antagonist (VKA) therapy who needed urgent surgery with significant bleeding risk. The registry record lists the condition as significant bleeding risk; further eligibility details are not reported in the registry record.
Intervention
OCTAPLEX, a four-factor prothrombin complex concentrate (4F-PCC), administered as an intravenous infusion.
Comparator
Beriplex P/N (Kcentra), also described as a 4F-PCC, administered as an intravenous infusion.
Primary question
The trial sought to assess whether OCTAPLEX's efficacy as a reversal agent was clinically non-inferior to Beriplex P/N (Kcentra). The primary endpoint was an adjudicated rating of hemostatic efficacy at the end of surgery. The registry record does not report the trial's primary outcome results, a non-inferiority margin, or an estimate of the between-group effect.
3. Trial Design
The record describes a Phase III, randomized, double-blind, multicenter study comparing OCTAPLEX with Beriplex P/N (Kcentra). It reports triple masking and an enrollment of 208. The study status is completed, with a start date of 2017-06-08 and a primary completion date of 2022-02-23. Octapharma is listed as the sponsor.
The interventions are named separately, and the arm descriptions identify intravenous infusions of each product. At the same time, the registry's design classification says single-group, which does not align with its descriptions of randomization and two intervention groups. The record does not explain this inconsistency, so the classification alone cannot clarify how participants were assigned or analyzed. Details about allocation procedures, concealment, and which roles were masked are not reported in the registry record.
The trial's stated purpose was to assess clinical non-inferiority of OCTAPLEX compared with Beriplex P/N (Kcentra) for reversal of VKA-induced anticoagulation in patients needing urgent surgery with significant bleeding risk. The primary outcome was assessed at the end of surgery. Secondary outcomes listed include INR measurement to ≤ 1.5, coagulation factor II, VII, IX, and X levels, and the number of patients requiring red blood cells. The record lists eight outcome measures but does not present their results.
Trial completion and the existence of a randomized design do not, by themselves, establish what the comparison found. The primary result, details of the statistical analysis, and information on analysis populations are 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
| Stage | Octaplex | Beriplex P/N (Kcentra) |
|---|---|---|
| STARTED | 105 | 103 |
| COMPLETED | 105 | 103 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Octaplex | Beriplex P/N (Kcentra) | Total |
|---|---|---|---|---|
| Participants analysed | 105 | 103 | 208 | |
| Age, Continuous | Years | 65.6 (31 to 90) | 66.8 (32 to 92) | 66.2 (31 to 92) |
| Sex: Female, Male: Female | Participants | 47 | 43 | 90 |
| Sex: Female, Male: Male | Participants | 58 | 60 | 118 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 105 | 102 | 207 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Pre-Infusion Anticoagulation Therapy: Sol. Fraxiparine (nadroparin calcium) | participants | 1 | 0 | 1 |
| Pre-Infusion Anticoagulation Therapy: Vitamin K Antagonist | participants | 105 | 103 | 208 |
| History of TEE: Presence of Embolic or Thrombotic Event | participants | 13 | 18 | 31 |
| History of TEE: Absence of Embolic or Thrombotic Event | participants | 92 | 85 | 177 |
| Type of Surgey: Cardiothoracic Surgery | participants | 5 | 4 | 9 |
| Type of Surgey: Orthopaedic Surgery | participants | 7 | 5 | 12 |
| Type of Surgey: Other Surgery Type | participants | 93 | 94 | 187 |
| Estimated Average Blood Loss: ≥200 mL | participants | 55 | 50 | 105 |
| Estimated Average Blood Loss: ≥100 mL but <200 mL | participants | 26 | 25 | 51 |
| Estimated Average Blood Loss: ≥50mL but <100 mL | participants | 24 | 28 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Hemostatic Efficacy Rating by IEAB, measured over At the end of the surgery.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was hemostatic efficacy at the end of surgery, rated by an Independent Endpoint Adjudication Committee (IEAB). It used a scale with categories of excellent, good, moderate, or none. The record defines excellent and good as effective hemostasis, and moderate and none as ineffective hemostasis. The assessment took account of blood loss and transfusion requirements in the context of the surgery, using objective criteria.
This kind of endpoint is intended to summarize whether bleeding was adequately controlled around the procedure while accounting for clinically relevant features of the surgical setting. The adjudication committee's role is to apply the stated criteria to endpoint assessments; the registry record does not give further details about adjudication procedures or whether assessors remained unaware of assigned treatment.
The registry identifies the outcome as a count of participants, but does not report the number classified as effective or ineffective in either group. It also does not give the distribution across the four rating categories, the endpoint analysis, or a treatment-effect estimate. The stated timeframe is at the end of surgery. Without the group results and analysis, the endpoint definition alone cannot establish the comparative efficacy finding.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison and defines an adjudicated primary endpoint, but it does not report the primary outcome counts or an analysis comparing OCTAPLEX with Beriplex P/N (Kcentra). It therefore does not provide an estimate of the treatment difference, its precision, or a result that can be interpreted against a non-inferiority criterion. The stated objective was non-inferiority, but the non-inferiority margin and the statistical conclusion are not reported in the registry record.
Non-inferiority is a specific statistical question: it asks whether the evidence is compatible with the new treatment being no worse than a prespecified acceptable margin relative to the comparator. General statistical interpretation requires both an estimated contrast and an uncertainty interval, considered against that margin. Neither the margin nor the endpoint analysis is reported, so no non-inferiority conclusion can be drawn from the registry description.
The primary outcome is a categorical assessment, with two categories defined as effective and two as ineffective. The registry record says the primary measure is a count of participants, but provides no group counts. Although enrollment is listed as 208, this number cannot substitute for outcome data or show how many participants contributed to the primary endpoint analysis. Group-specific analysis denominators are not reported in the registry record.
The record lists secondary outcomes concerning INR, coagulation factor levels, and red blood cell requirements, but does not report their findings. The presence of a list of outcomes indicates what was intended to be measured, not what was observed. No conclusion about differences in those outcomes can be made from their names alone.
The adverse-event information is separate from the primary efficacy result. The record lists serious adverse events, other adverse-event counts, deaths, and several serious-event terms. These counts do not establish that an event was caused by either study treatment, and the registry record does not report comparative safety analyses or further context for the events. The figures should therefore be read as descriptive registry entries, not as a complete assessment of comparative benefit or risk.
Overall, the posted record supports a description of the trial's stated question, design labels, endpoint definition, and selected safety counts. It does not report enough outcome or analysis information to judge the comparative primary result. That absence should be distinguished from a finding of no difference: no primary comparison is reported in the registry record.
9. Statistical Methods Explained
What does a randomized comparison aim to estimate?
In general, random assignment is intended to make the treatment groups comparable at the time of assignment, reducing the risk that measured or unmeasured baseline differences determine the comparison. The effect estimate still depends on how outcomes, follow-up, and analysis populations are defined and handled. The registry record labels this trial randomized, but does not report the randomization procedure, allocation concealment, or the analysis used for the primary endpoint. Its single-group model classification also conflicts with its description of randomized allocation and two intervention groups; the reason is not reported in the registry record.
How should a categorical primary endpoint be analyzed?
General statistical explanation: when an endpoint classifies participants into outcome categories, an analysis can compare the distributions or the proportion assigned to a prespecified category. The choice depends on the endpoint definition and the planned estimand. Here, the record defines excellent and good ratings as effective hemostasis, and moderate and none as ineffective. It also describes the measure as a participant count. But the group-specific counts, the planned contrast, and the statistical method are not reported in the registry record. It is therefore not possible to reconstruct or assess the primary comparison.
What is special about a non-inferiority question?
General statistical explanation: a non-inferiority analysis evaluates whether the treatment effect is sufficiently favorable relative to a prespecified margin, rather than simply asking whether a conventional test detects a difference. The margin sets the largest difference that would still meet the trial's definition of non-inferiority. Interpretation ordinarily needs the margin, the estimated treatment contrast, and its confidence interval, along with the direction in which the contrast is defined. The record gives the trial's non-inferiority objective but does not report the margin, the contrast, the interval, or the conclusion. It does not report the statistical plan, either.
A confidence interval is a range of estimates compatible with the data under the statistical model and its assumptions. General explanation: a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. In a non-inferiority setting, the interval's position relative to the prespecified margin is central to interpretation. No interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.
Why do denominators and analysis populations matter?
General statistical explanation: an outcome count is interpretable only in relation to the group of participants eligible for that analysis. The number randomized, the number treated, and the number included in an endpoint analysis may differ. Missing endpoint assessments, exclusions, and analysis-population definitions can affect the result and its interpretation. The record lists enrollment as 208, but does not report primary-endpoint denominators, missing outcome counts, or analysis-population definitions. It is not possible to determine from the registry entry how those issues were handled.
What does the planning illustration represent?
The registry record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes planning for a chosen proportion of the observed effect. Such sample-size calculations are hypothetical planning exercises, not observed trial outcomes and not observed power. The record does not provide numerical sample-size illustration results in the registry record for this analysis. The trial's own sample-size justification and design assumptions are not reported in the registry record. In particular, the planning illustration should not be treated as evidence that the trial was designed around any particular effect or that its primary question was answered.
How should multiplicity and secondary outcomes be considered?
General statistical explanation: when a study evaluates multiple outcomes or several comparisons, the chance of a nominally unusual result can increase unless the analysis plan addresses multiplicity. The registry lists several secondary outcomes, but does not report an adjustment strategy, a hierarchy of tests, or results. It also lists no registry analyses. That absence does not establish that analyses were not conducted; it means the registry record does not report them. Consequently, neither the inferential status of secondary findings nor their relationship to the primary question can be assessed.
The methods available in the record are therefore limited to the design labels, endpoint description, listed secondary outcomes, and planning assumptions. The methods used to estimate the primary effect, quantify uncertainty, handle missing observations, and assess the non-inferiority objective are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures and identifies a primary hemostatic efficacy endpoint alongside secondary measures for INR, coagulation factor levels, and red blood cell requirements. However, it reports no registry analyses. This means the record does not present results or describe how the multiple outcomes were handled; it does not establish that no analyses were performed.
A statistical plan for multiplicity—such as an order for testing outcomes or an adjustment to account for multiple comparisons—is not reported in the registry record. Without that information and without outcome results, the evidential status of any secondary finding cannot be assessed. The primary result itself is not reported, so there is no basis for determining whether secondary outcomes were considered confirmatory, exploratory, or otherwise qualified.
Information about missing data is also not reported in the registry record. It does not give the number of participants with an observed primary outcome, reasons for missing assessments, or methods used to handle missingness. The analysis populations are not described, and the record does not specify how participants who did not complete the planned assessment were treated in an analysis.
These omissions matter because the interpretation of an endpoint depends not only on its definition, but also on who contributed data and how incomplete observations were handled. The reported enrollment cannot be assumed to equal the primary analysis population. The record also does not provide an analysis plan with which to compare the reported results, because primary and secondary analyses are not reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Octaplex | 13 | 105 | 12.4% |
| Beriplex P/N (Kcentra) | 6 | 103 | 5.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Octaplex | 5 of 105 |
| Beriplex P/N (Kcentra) | 1 of 103 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Octaplex | 86 of 105 |
| Beriplex P/N (Kcentra) | 80 of 103 |
Most frequent serious adverse event terms
| Event term | Organ system | Octaplex | Beriplex P/N (Kcentra) |
|---|---|---|---|
| Angina Unstable | Cardiac disorders | 1 of 105 | 0 of 103 |
| Cardiac Failure Chronic | Cardiac disorders | 1 of 105 | 0 of 103 |
| Myocardial Ischaemia | Cardiac disorders | 1 of 105 | 0 of 103 |
| Anaemia | Blood and lymphatic system disorders | 0 of 105 | 1 of 103 |
| Haemorrhagic Anaemia | Blood and lymphatic system disorders | 0 of 105 | 1 of 103 |
| Cardiac Failure Acute | Cardiac disorders | 0 of 105 | 1 of 103 |
| Pneumonia | Infections and infestations | 0 of 105 | 1 of 103 |
| Gastritis Erosive | Gastrointestinal disorders | 1 of 105 | 0 of 103 |
| Mesenteric Haematoma | Gastrointestinal disorders | 1 of 105 | 0 of 103 |
| Proctitis | Gastrointestinal disorders | 1 of 105 | 0 of 103 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Octaplex | Beriplex P/N (Kcentra) |
|---|---|---|---|
| Procedural Pain | Injury, poisoning and procedural complications | 50 of 105 | 50 of 103 |
| Asthenia | General disorders | 13 of 105 | 18 of 103 |
| Postoperative Wound Complications | Injury, poisoning and procedural complications | 15 of 105 | 15 of 103 |
| Anaemia | Blood and lymphatic system disorders | 6 of 105 | 6 of 103 |
| Cardiac AEs | Cardiac disorders | 5 of 105 | 7 of 103 |
| Metabolism and nutrition disorders | Metabolism and nutrition disorders | 4 of 105 | 7 of 103 |
| Abdominal Pain | Gastrointestinal disorders | 3 of 105 | 5 of 103 |
| Nervous System Disorders | Nervous system disorders | 6 of 105 | 1 of 103 |
| Dysuria | Renal and urinary disorders | 5 of 105 | 2 of 103 |
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | 2 of 105 | 5 of 103 |
Serious events with the highest arm-level rate: anaemia (1.0%), haemorrhagic anaemia (1.0%), cardiac failure acute (1.0%), pneumonia (1.0%), gastritis haemorrhagic (1.0%).
The registry lists serious adverse events for 13 of 105 participants at risk in the Octaplex group and 6 of 103 participants at risk in the Beriplex P/N (Kcentra) group. It lists other adverse-event counts of 86 of 105 and 80 of 103, respectively. Deaths are listed as 5 in the Octaplex group and 1 in the Beriplex P/N (Kcentra) group. These are counts as recorded, not a treatment-effect analysis.
The registry also lists Anaemia, Haemorrhagic Anaemia, Cardiac Failure Acute, Pneumonia, Gastritis Haemorrhagic, and Ileus among the top serious terms, each with a reported value of 1.0%. The record does not provide group-specific values for these terms in the registry entries, so they should not be assigned to a particular group.
These entries do not establish that an event was caused by treatment. The registry information does not report event timing, severity beyond the serious-event classification, exposure duration, adjusted comparisons, or a fuller account of how events were collected. The figures are therefore descriptive safety information, not a complete comparative safety evaluation.
12. What the Result Does, and Does Not, Mean
The trial's stated objective was to determine whether OCTAPLEX was clinically non-inferior to Beriplex P/N (Kcentra) as a reversal agent for VKA-induced anticoagulation in patients needing urgent surgery with significant bleeding risk. The primary outcome was an adjudicated assessment of hemostatic efficacy at the end of surgery, with the rating categories defined in the registry record.
What the record does not establish is the comparative primary result. It does not report the number of participants with effective hemostasis in either group, an effect estimate, a confidence interval, or a non-inferiority margin. Consequently, it cannot support a conclusion that OCTAPLEX met or failed the stated non-inferiority objective. The lack of a reported result is not evidence that the treatments had identical outcomes, nor does it establish that one was superior.
The record also does not report results for its listed secondary outcomes, including INR, coagulation factor levels, and red blood cell requirements. Their inclusion in the outcome list does not show whether they favored either group, how precisely they were estimated, or whether they were analyzed according to a prespecified plan.
The safety counts offer descriptive information about serious and other adverse events and deaths in the groups. They do not by themselves identify causes, account for differences in exposure or follow-up, or provide a formal estimate of comparative safety. A complete interpretation would require the context and analysis that are not reported in the registry record.
In short, the registry record identifies a clinically focused comparative question and describes how the primary endpoint was categorized. It does not report the outcome evidence needed to answer that question. The distinction is important: a trial's design and endpoint definition describe what was intended to be studied, while an efficacy or safety conclusion requires reported results and an appropriate analysis.
13. Why This Trial Matters Statistically
This trial is statistically notable for its non-inferiority objective. General explanation: unlike a simple test for any difference, non-inferiority requires a prespecified boundary that defines how much worse the experimental treatment could be while still meeting the study's criterion. A result must be interpreted with respect to that boundary and the uncertainty around the estimated comparison. The registry record states the objective but does not report the margin, primary estimate, interval, or conclusion.
The primary endpoint also combines clinical judgment with objective criteria. It is assessed by an independent endpoint committee and considers blood loss and transfusion requirements in the context of surgery. The registry defines which rating categories count as effective, but does not provide the underlying group results. This makes the endpoint definition informative about the trial question, while leaving the answer to that question unavailable in the record.
The record's conflicting design labels also merit attention. It describes randomized allocation, masking, and two intervention groups, but classifies the model as single-group. Since the record does not explain the discrepancy, readers cannot resolve it using the registry description alone. This does not invalidate the stated trial purpose, but it limits confidence in a simple reading of the design fields.
Finally, the listed safety counts and secondary outcomes illustrate why endpoint-specific results and analysis details matter. Counts alone do not convey uncertainty, causation, or comparative effects, and a list of secondary outcomes does not substitute for results or a multiplicity plan. The registry entry therefore offers useful design and endpoint context, but not enough statistical evidence to judge the primary comparison.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation for interpretation is that the registry record does not report the primary endpoint results or an efficacy analysis. It gives the endpoint definition and timeframe, but not the group counts, effect estimate, precision interval, or non-inferiority margin. The primary statistical conclusion is therefore unavailable.
The design description is internally inconsistent: allocation is listed as randomized and two intervention arms are described, while the model is listed as single-group. No explanation is reported in the registry record. Further information about the allocation procedure, masking roles, protocol, and statistical analysis plan is also not reported.
Although the record lists an enrollment of 208, it does not give endpoint-specific denominators or analysis populations. Missing data, reasons for incomplete assessments, and methods for handling them are not reported. The record also does not report a multiplicity strategy for the several listed outcome measures or results for the secondary outcomes.
The adverse-event entries are limited to counts and selected serious-event terms. The registry record does not provide additional context on timing, exposure, attribution, or comparative analysis. These limitations mean the listed safety information cannot by itself resolve comparative safety, just as the study's stated objective cannot substitute for the missing primary result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk. — NCT02740335.
- Registry record last updated 2023-03-08; status last verified 2023-03.
- Results first posted 2023-03-08.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed Phase III, randomized, double-blind, multicenter study sponsored by Octapharma. It lists triple masking and an enrollment of 208. The recorded start date is 2017-06-08, and the primary completion date is 2022-02-23.
The study compared intravenous OCTAPLEX with intravenous Beriplex P/N (Kcentra) for reversal of VKA-induced anticoagulation in patients needing urgent surgery with significant bleeding risk. Its primary endpoint was an IEAB rating of hemostatic efficacy at the end of surgery. The registry states that excellent and good ratings counted as effective, while moderate and none counted as ineffective.
The record also lists secondary outcomes and selected adverse-event counts. It classifies the study model as single-group despite describing randomized allocation and two intervention groups. The primary outcome results, statistical analysis, non-inferiority margin, and analysis populations are not reported in the registry record.