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 Active-control Randomized Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (NCT05523297), a randomized phase 3 study. The primary outcome is Number of Patients Requiring Additional Hemostatic Intervention.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05523297 |
| Phase | Phase 3 |
| Condition | Bleeding Cardiac Surgery Patients |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 420 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
Adults undergoing cardiac surgery who were bleeding. The registry record describes a multicenter trial and lists the condition as bleeding cardiac surgery patients. It does not report further eligibility details or a more specific description of the population used for the primary outcome.
Intervention
Octaplex, a 4-factor prothrombin complex concentrate. The record describes a recommended initial dose that varied by body weight and the possibility of a second dose when bleeding and suspected coagulation deficiency continued. Further dosing details are not reported in the registry record.
Comparator
Frozen plasma, also described as FP. The record describes a recommended initial dose that varied by body weight and the possibility of a second dose under specified ongoing bleeding and coagulation-deficiency conditions. The comparison is active-control rather than placebo-controlled.
Primary question
How many participants required additional hemostatic intervention from 60 minutes to 24 hours after the first dose of study treatment? The endpoint definition calls the response effective when no additional hemostatic intervention was required during that interval. Comparative outcome counts and an effect estimate are not reported in the registry record.
3. Trial Design
The trial is a prospective, multicenter, active-control, randomized Phase 3 study with a parallel-group design. The registry record identifies double masking, although it does not specify which groups of people were masked. The intervention groups were Octaplex and frozen plasma. The sponsor is Octapharma.
The record reports enrollment of 420 and states that participants were randomized at 12 hospitals. The trial status is completed. Its recorded start date is 2022-11-30, and its primary completion date is 2024-06-27. These dates describe the registry record; they do not establish when results were analyzed or submitted.
The intervention descriptions include weight-based recommended initial doses and allow for a second dose in specified circumstances. They also refer to continued bleeding and suspected coagulation deficiency. The registry record does not provide further details about treatment delivery, allocation concealment, masking procedures, protocol deviations, or adherence.
The endpoint list includes the primary measure and secondary measures concerning additional hemostatic intervention, hemoglobin levels, chest tube drainage, bleeding severity, and transfusion. The record lists 29 outcome measures and 53 analyses. Those counts indicate a broad set of planned or reported outcome analyses, but do not establish which results were statistically significant or how the analyses were prioritized beyond the designation of the primary outcome.
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: Of 538 enrolled participants, 420 met the inclusion criteria and were randomized to treatment.
Overall Study
| Stage | Octaplex | Frozen Plasma |
|---|---|---|
| STARTED | 213 | 207 |
| Per-protocol Population (PP) | 209 | 200 |
| COMPLETED | 204 | 198 |
| NOT COMPLETED | 9 | 9 |
Reasons for not completing this period:
| Reason | Octaplex | Frozen Plasma |
|---|---|---|
| Death | 7 | 8 |
| Lost to Follow-up | 2 | 1 |
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 | Frozen Plasma | Total |
|---|---|---|---|---|
| Participants analysed | 213 | 207 | 420 | |
| Age, Continuous | years | 63.97 (SD 13.596) | 61.68 (SD 14.002) | 62.84 (SD 13.829) |
| Sex: Female, Male: Female | Participants | 56 | 55 | 111 |
| Sex: Female, Male: Male | Participants | 157 | 152 | 309 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 2 | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 132 | 132 | 264 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 79 | 73 | 152 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): Asian | Participants | 20 | 21 | 41 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 3 | 5 |
| Race (NIH/OMB): White | Participants | 138 | 137 | 275 |
| Race (NIH/OMB): More than one race | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 49 | 45 | 94 |
| Body Height | centimeter (cm) | 171.03 (SD 10.082) | 171.83 (SD 10.565) | 171.42 (SD 10.318) |
| Body Weight | kilogram (kg) | 84.63 (SD 19.344) | 83.62 (SD 19.520) | 84.13 (SD 19.414) |
| Body Mass Index (BMI) | kilogram per square meter (kg/m²) | 28.88 (SD 5.986) | 28.20 (SD 5.403) | 28.55 (SD 5.710) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Requiring Additional Hemostatic Intervention, measured over 60 minutes to 24 hours after first dose of IMP.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants requiring additional hemostatic intervention from 60 minutes to 24 hours after initiation of the first dose of study treatment. The registry definition describes a response as effective when no such intervention is required in that interval.
Additional intervention is defined broadly. It includes systemic hemostatic agents, such as platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII, other coagulation factor products, or a second dose of study treatment. It also includes hemostatic procedures such as surgical reopening for bleeding. The endpoint therefore represents whether further intervention was needed, rather than a direct laboratory measurement alone.
In general, an endpoint of this kind can capture whether initial treatment was followed by a need for further clinical action. Its interpretation depends on the stated time window and the intervention criteria. Because the definition includes decisions about whether to administer products or perform a procedure, the measure combines clinical events with treatment decisions. The registry record does not report primary endpoint counts by group, a comparative effect estimate, or the uncertainty around that estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available record establishes the trial question, design, endpoint definition, and selected safety counts. It does not report comparative primary-outcome results. In particular, the registry record does not report the number of participants in each treatment group who required additional hemostatic intervention, an effect estimate, a confidence interval, or a p-value for that endpoint. The direction and precision of the primary comparison therefore cannot be assessed from these registry entries.
The definition of effectiveness is based on not requiring further intervention during the interval from 60 minutes to 24 hours after the first dose. That definition should be kept distinct from a claim about the overall course of bleeding, transfusion needs, or other outcomes. The record lists secondary outcomes on related topics, but does not include their comparative results in the registry record for this analysis.
The safety information reports participants at risk and affected by serious adverse events, other adverse events, and deaths in each group. Those are descriptive counts, not evidence by themselves that an event was caused by treatment. The record also lists serious adverse-event terms and percentages. It does not provide additional context for interpreting those percentages, such as treatment-specific rates for each listed term or an adjusted comparison.
In general, a comparative treatment estimate is easier to interpret when presented with an uncertainty interval and a clearly defined analysis population. A confidence interval describes a range of estimates compatible with the data and statistical model; its width conveys precision. No primary-outcome interval is reported in the registry record. The absence of a reported estimate is not evidence that the groups had the same result, and it does not establish that either treatment was better.
The record identifies randomization and double masking, which describe important aspects of trial design, but design features alone do not substitute for outcome results. A sound reading must distinguish what the study set out to compare from what the posted results actually quantify. Here, the registry entry supports a description of the comparison and its endpoint, but not a conclusion about the comparative primary outcome.
9. Statistical Methods Explained
The registry record identifies this as a randomized, parallel-group trial, but does not report the detailed statistical analysis plan. The distinctions below explain general statistical concepts relevant to interpreting this kind of study; they should not be read as a description of analyses that the investigators necessarily performed.
What does randomization contribute?
In general, randomization assigns participants to treatment groups by chance. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that are known and those that are not measured. It does not guarantee that every characteristic will be balanced, and it does not replace reporting how participants were analyzed or what outcomes occurred. The registry record does not report allocation concealment procedures or baseline characteristics in the registry record.
The parallel-group design means the treatment groups are followed as separate groups rather than participants crossing from one assigned treatment to another as part of the design. The registry identifies double masking, but does not specify who was masked or how masking was maintained. Those details matter when interpreting outcomes that can involve clinical judgment, including whether additional hemostatic intervention is required.
How should a binary endpoint be understood?
The primary measure is described as a count of participants requiring additional intervention. This is an event-based outcome: a participant either meets the endpoint definition during the stated window or does not. In general, such an outcome can be summarized using counts and a comparison of the chance of an event between groups. The registry record does not report the group counts or a comparative estimate for this endpoint, so no numerical comparison can be interpreted.
The endpoint's operational definition is central. It includes additional systemic agents and procedures, including a second dose of study treatment or surgical reopening for bleeding. A difference in this endpoint, if reported, would concern the defined need for further intervention during the stated period. It would not automatically answer questions about other outcomes, or establish the mechanism behind any observed group difference.
What do estimates and uncertainty convey?
In general, an effect estimate expresses the observed comparison between groups on a defined scale. A confidence interval conveys uncertainty around that estimate under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but precision is not the same as clinical importance. A p-value, when reported, describes how compatible the observed data are with a specified null hypothesis under the statistical model; it is not the probability that the null hypothesis is true. None of these primary comparison results is reported in the registry record.
Without the estimate and its uncertainty, it is not possible to assess the magnitude, direction, or precision of the primary comparison. The enrollment figure alone does not provide that information. Nor can the safety counts be used to reconstruct the missing primary endpoint, because they describe different outcomes.
Why can outcome definitions and analysis populations matter?
In general, the analysis population determines which randomized participants contribute to a result. An intention-to-treat analysis commonly retains participants in their assigned groups, while other approaches may use different eligibility or treatment-completion rules. These choices can affect interpretation, especially when participants have incomplete outcome information or do not follow assigned treatment. The registry record does not report the analysis population for the primary endpoint, how missing outcome data were handled, or whether sensitivity analyses were conducted.
Outcome timing also matters. The primary endpoint is defined over a window beginning 60 minutes after the first dose and ending 24 hours after it. Results for another time window would answer a different question. The record does not report whether endpoint assessments were independently adjudicated or how disagreements about intervention classification were resolved.
What can be said about planning assumptions?
The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect, but no illustration values are included in the registry record for this analysis. Such sample-size figures, when reported, are planning illustrations and not observed power. They do not replace the trial's outcome estimates, confidence intervals, or analysis plan. The registry record does not report the trial's own sample-size justification or its full statistical design assumptions.
In general, planning calculations depend on assumptions about the effect to be detected, variability or event frequency, significance level, allocation, and analysis method. A calculation based on an observed effect is especially dependent on that effect estimate and should not be read as proof that the trial had a particular probability of detecting a real effect. No additional calculation can be reconstructed from the registry entries without inventing inputs.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 29 outcome measures and 53 analyses. A broad outcome and analysis set raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase if the tests are treated as independent opportunities to declare a finding. Statistical strategies can address multiplicity, for example by prioritizing outcomes or adjusting inference, but the appropriate approach depends on the prespecified analysis plan.
The multiplicity strategy is not reported in the registry record. The record also does not report which secondary analyses were prespecified, whether analyses were exploratory, how outcomes were hierarchically ordered, or whether any adjustment was applied. The number of analyses alone does not establish that an error occurred, nor does it determine the evidential strength of any particular result.
Missing-data handling and analysis populations are also not reported in the registry record. The registry entries do not describe the number of participants with missing primary endpoint information, reasons for missingness, exclusions after randomization, or sensitivity analyses. In general, missing outcomes can affect interpretation when the likelihood of missingness is related to treatment or outcome status. The analysis population and missing-data method should therefore be considered alongside the estimate and its uncertainty, if those results are reported.
These omissions limit assessment of how robust the primary and secondary inferences are. They do not justify assuming that data were missing or that analyses were selectively reported; those details are simply not reported in the registry record.
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 | 77 | 213 | 36.2% |
| Frozen Plasma | 98 | 207 | 47.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Octaplex | 7 of 213 |
| Frozen Plasma | 8 of 207 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Octaplex | 206 of 213 |
| Frozen Plasma | 201 of 207 |
Most frequent serious adverse event terms
| Event term | Organ system | Octaplex | Frozen Plasma |
|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 7 of 213 | 8 of 207 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 4 of 213 | 11 of 207 |
| Acute kidney injury | Renal and urinary disorders | 4 of 213 | 10 of 207 |
| Cardiac tamponade | Cardiac disorders | 8 of 213 | 5 of 207 |
| Atrioventricular block complete | Cardiac disorders | 9 of 213 | 3 of 207 |
| Cardiogenic shock | Cardiac disorders | 3 of 213 | 8 of 207 |
| Post procedural hemorrhage | Injury, poisoning and procedural complications | 2 of 213 | 7 of 207 |
| Cerebrovascular accident | Nervous system disorders | 3 of 213 | 5 of 207 |
| Cardiac failure congestive | Cardiac disorders | 2 of 213 | 5 of 207 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 213 | 5 of 207 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Octaplex | Frozen Plasma |
|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 87 of 213 | 64 of 207 |
| Anemia | Blood and lymphatic system disorders | 65 of 213 | 66 of 207 |
| Hypervolemia | Metabolism and nutrition disorders | 39 of 213 | 42 of 207 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 28 of 213 | 42 of 207 |
| Edema peripheral | General disorders | 33 of 213 | 28 of 207 |
| Acute kidney injury | Renal and urinary disorders | 21 of 213 | 36 of 207 |
| Hypotension | Vascular disorders | 17 of 213 | 26 of 207 |
| Nausea | Gastrointestinal disorders | 23 of 213 | 15 of 207 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 28 of 213 | 8 of 207 |
| Hemoglobin decreased | Investigations | 16 of 213 | 16 of 207 |
Serious events with the highest arm-level rate: respiratory failure (5.3%), acute kidney injury (4.8%), atrioventricular block complete (4.2%), atrial fibrillation (3.9%), cardiogenic shock (3.9%).
The registry record reports serious adverse events among participants at risk in each group. In the Octaplex group, 77 participants were affected among 213 at risk. In the Frozen Plasma group, 98 participants were affected among 207 at risk. The record also reports other adverse events among 206 participants in the Octaplex group, with 213 at risk, and among 201 participants in the Frozen Plasma group, with 207 at risk. Deaths are reported for 7 participants in the Octaplex group and 8 in the Frozen Plasma group.
These figures are descriptive. They do not establish that an event was caused by a treatment, and they should not be treated as a comparative safety analysis without the relevant definitions, follow-up details, and statistical comparisons. The record lists respiratory failure at 5.3%, acute kidney injury at 4.8%, atrioventricular block complete at 4.2%, atrial fibrillation at 3.9%, cardiogenic shock at 3.9%, and cardiac tamponade at 3.8% among the listed serious adverse-event terms. Treatment-specific counts for those terms are not reported in the registry record.
General safety interpretation also depends on the event definitions, surveillance period, seriousness criteria, and whether repeated events are counted as events or affected participants. Those details are not reported in the registry record for this analysis. The counts should therefore be read as registry-reported safety summaries, not as proof of a treatment effect or absence of risk.
12. What the Result Does, and Does Not, Mean
The record describes a clinically focused randomized comparison in bleeding adult cardiac surgery patients: Octaplex versus frozen plasma, with additional hemostatic intervention during a defined post-dose interval as the primary endpoint. The endpoint is meaningful as a measure of whether further hemostatic treatment or a procedure was required, according to the registry's stated criteria.
The registry entries do not report the primary outcome results by group or a comparative estimate. Consequently, they cannot establish the size or direction of a difference, how precise an estimate would be, or whether the data are compatible with a range of clinically important effects. They also do not support a conclusion that the treatments are equivalent. Lack of a reported estimate is not evidence of no difference.
The primary endpoint should not be conflated with the secondary outcomes listed in the registry, which include chest tube drainage, bleeding severity, hemoglobin-related assessment, and transfusion measures. Each outcome addresses a distinct aspect of clinical response. Results for one outcome, if available, would not automatically settle the others.
The safety counts describe serious and other adverse events and deaths by treatment group, but they do not identify causation. The listed serious adverse-event terms and percentages add context to the safety record, yet the registry entries do not provide treatment-specific comparative results for those terms. A complete benefit-risk interpretation would require the outcome estimates, their uncertainty, analysis details, and fuller safety context.
In general, randomized design can strengthen a treatment comparison by reducing confounding at assignment, but the design label alone does not answer the clinical question. The registry record supports a careful account of what was studied and how the primary endpoint was defined. It does not support a treatment recommendation or a claim that either intervention did or did not work.
13. Why This Trial Matters Statistically
This trial is statistically relevant because it uses random allocation to compare an active hemostatic treatment with frozen plasma in adults bleeding during cardiac surgery. The comparison is framed around a concrete clinical action: whether participants require additional intervention after the initial dose. The endpoint definition makes clear that the outcome includes both additional products and procedural intervention.
The record also illustrates why a trial's design and its results must be read separately. Randomization, double masking, a parallel-group structure, and multicenter conduct describe how the study was organized. They do not reveal the primary outcome estimate. Without group-specific primary outcome counts and an uncertainty measure, readers cannot judge the magnitude or precision of the treatment comparison.
The listed secondary outcomes broaden the clinical questions to bleeding, drainage, and transfusion. The record's 29 outcome measures and 53 analyses also make transparency about prespecification and multiplicity important. Those details are not reported in the registry record. Their absence limits the ability to assess how the analysis plan distinguished confirmatory questions from exploratory ones.
The safety summaries are another reason to distinguish descriptive reporting from causal inference. Counts of affected participants and deaths provide information about events recorded in the groups, but interpretation depends on definitions, follow-up, and comparative analyses. This record therefore offers an instructive example of how trial registration and outcome reporting can establish a study's scope while leaving important questions about comparative results and statistical certainty unanswered.
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.
A central limitation for interpreting this trial from the registry record is that comparative primary endpoint results are not reported in the registry record for this analysis. The endpoint definition is detailed, but group-specific counts, an effect estimate, a confidence interval, and a p-value are not included. This prevents assessment of effect direction, magnitude, and precision.
The registry identifies double masking but does not say which people were masked or describe the procedures used to preserve masking. It reports randomization but does not describe allocation concealment. These omissions limit evaluation of how assignment and outcome assessment were implemented. They do not establish that implementation was inadequate.
The primary endpoint includes decisions about additional systemic hemostatic agents and procedures. In general, this kind of composite clinical-action outcome may reflect both the participant's condition and clinician decisions. The record does not report adjudication procedures, consistency of intervention thresholds across hospitals, or the analysis population used for this endpoint.
The registry lists many outcome measures and analyses, but the multiplicity strategy, missing-data methods, prespecified analysis hierarchy, and sensitivity analyses are not reported in the registry record. The safety summaries also lack treatment-specific results for the listed serious adverse-event terms. These reporting gaps constrain statistical interpretation; they do not by themselves show bias, missing data, or selective reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Active-control Randomized Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery — NCT05523297.
- Registry record last updated 2025-08-15; status last verified 2025-08.
- Results first posted 2025-08-15.
- 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
This completed, randomized, double-masked, parallel-group Phase 3 trial compared Octaplex with frozen plasma in bleeding adult cardiac surgery patients. It was prospective and multicenter, with enrollment of 420 and randomization at 12 hospitals. The recorded start date is 2022-11-30, and the primary completion date is 2024-06-27. Octapharma is listed as sponsor.
The primary endpoint counts participants requiring additional hemostatic intervention from 60 minutes to 24 hours after the first dose. The registry record also lists secondary bleeding and transfusion outcomes and reports safety counts by group. Comparative primary endpoint results, detailed analysis populations, missing-data methods, and multiplicity procedures are not reported in the registry record. The available information therefore describes the study and its endpoint, but does not establish a comparative primary-outcome effect.