An Open Enrollment Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Enrollment Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency (NCT00945906), a na phase 3 study. The primary outcome is Adverse Events.

2. Clinical Question

The registry describes the purpose as providing Factor XIII concentrate while the product was not yet commercially available in the United States. The stated follow-up began after the first infusion and continued until study completion, which was up to 2 years or until the product became commercially available in the USA. The study was prospective, multicenter, open enrollment, and Phase 3. These features help describe the setting, but they do not create a control comparison. The safety counts are therefore best read as observations from a treated group under the study’s conditions, not as estimates of what would have occurred without treatment.

3. Trial Design

This was a prospective, multicenter, open-enrollment Phase 3 study of human plasma-derived Factor XIII concentrate in people with congenital Factor XIII deficiency. The registry lists a single-group model, no masking, and allocation as not applicable. Enrollment was 61. The study is recorded as completed; its listed start was 2009-09 and its primary completion was 2011-08.

All participants in the study group received the intervention, FXIII Concentrate (Human), by intravenous infusion approximately every 28 days. The arm description says dosing was intended to maintain a trough Factor XIII level of approximately 5 to 20%. The registry summary describes close follow-up, including assessment of dose and bleeding-related outcomes. However, the registry record does not report enough detail to reconstruct all treatment adjustments or follow-up procedures.

Without a separate control group, the design can describe events observed among participants treated with Factor XIII concentrate, but it cannot directly estimate a randomized treatment-versus-control effect. Open-label status also means the record does not describe masking of participants or study personnel. These features are important when considering how events were reported, assessed, and attributed to treatment.

The listed primary endpoint was adverse events. Secondary outcomes included hematology and chemistry testing, Factor XIII antibody testing, Factor XIII concentration, the number of participants with at least one bleeding episode, and the number of bleeding episodes. The registry lists 6 outcome measures and 0 analyses. A full statistical plan, including prespecified analysis methods and any interim analyses, is not reported in the registry record. The study description and outcome listings therefore establish what was intended to be assessed, while leaving important details about the analysis approach unspecified.

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:

Analysis population for the primary outcome, as defined in the registry: The Safety Population consisted of all subjects who received a dose of Factor XIII Concentrate (Human) during the study. Treatment related AEs are events whose relationship to study treatment is related, or possibly related, in the opinion of the investigator. AEs with missing relationship are considered related to treatment.

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 Adverse Events, measured over After the first infusion until study completion. Study completion is up to 2 years or until Factor XIII Concentrate (Human) is commercially available in the USA..

The primary endpoint counted participants with any treatment-emergent adverse event, treatment-related adverse event, or serious adverse event. The timeframe began after the first infusion and continued until study completion, which was up to 2 years or until Factor XIII Concentrate (Human) became commercially available in the USA. The Safety Population consisted of participants who received a dose during the study.

A participant-based safety count is useful because it indicates how many people experienced an event in a defined category during follow-up. It differs from a count of all event episodes: a person with repeated events may still contribute to a participant count once within a category. The registry’s definition also distinguishes treatment-emergent events from those judged related or possibly related to treatment, and includes events with missing relationship in the treatment-related definition.

Safety monitoring is relevant in a treatment study because it records harms and tolerability concerns observed during exposure. The endpoint does not, by itself, show whether an event was caused by treatment. Nor does a participant count describe event timing, duration, severity beyond the serious-event classification, or the clinical course. Those details are not reported in the registry record. The listed endpoint is therefore a broad safety measure rather than a single, narrowly defined event or a comparative estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and lists adverse events as the primary outcome. The reported safety results are counts of participants, not a comparison of event rates between randomized groups. This distinction determines which statistical interpretations are available: a count can describe what was observed in the treated group, but without a comparison group it cannot isolate a treatment effect from other explanations.

What does a participant count measure?

A participant count records whether people experienced an event within a specified category during the stated follow-up. It is different from counting every event episode. If a participant experiences more than one episode, an episode count can include each occurrence, while a participant count represents whether that person met the endpoint. The registry lists both participant-based adverse-event measures and secondary outcomes concerning the number of bleeding episodes, but outcome results for the latter are not reported in the registry record.

The safety endpoint combines broad categories: treatment-emergent adverse events, treatment-related adverse events, and serious adverse events. These categories are not interchangeable. Treatment-emergent describes events observed after exposure begins within the endpoint timeframe; treatment-related reflects an attribution judgment; serious is a classification of the event. The registry defines treatment-related events to include those judged related or possibly related by the investigator, as well as events with missing relationship. The record does not provide event-level detail to examine how these definitions applied in each case.

Why does the single-group design matter?

In a randomized comparison, a treatment group and a control group can be contrasted under the study’s allocation process. Here, allocation is listed as not applicable and the model is single-group. The observed counts therefore have no concurrent randomized reference. Differences from an external expectation, if considered, would depend on assumptions and information not reported in the registry record. A within-group count alone is not a causal comparison.

Open-label status means masking is listed as none. In general, knowing the treatment can affect reporting, clinical assessment, and decisions about whether an event is related to treatment. That possibility does not show that a specific event was misclassified; it is a design consideration when interpreting subjective judgments. The registry record does not report procedures that would allow an assessment of the influence of knowledge of treatment.

What would an uncertainty interval add?

General: a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified analysis. It helps readers distinguish a relatively precise estimate from one compatible with a broad range of values. For a single-group participant count, an interval could describe uncertainty around a proportion if the denominator, analysis method, and assumptions were specified. The registry record does not report confidence intervals or an inferential analysis for these safety counts, so no such precision estimate can be attributed to the posted results.

General: a hypothesis test addresses a defined statistical question and depends on a specified null hypothesis, outcome, and analysis plan. A p-value does not measure the probability that treatment works or that a result is due to chance. No hypothesis test or comparative analysis is reported for the adverse-event results. The registry lists 0 analyses, and the statistical plan is not reported in the registry record.

Why can follow-up and exposure matter?

General: counts of participants with an event may be affected by how long participants are observed and how much time they are exposed to treatment. A participant followed longer has more opportunity for an event to be recorded. Time-to-event or exposure-adjusted methods can address some questions about event timing or person-time, but they require suitable data and a defined analysis. The registry’s stated follow-up was after the first infusion until study completion, up to 2 years or until commercial availability in the USA. It does not report the distribution of individual follow-up or exposure time, so such analyses cannot be reconstructed from the stated counts.

The sample-size illustrations use a general planning framework rather than the study’s documented design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The study itself is single-group, so this hypothetical two-arm setup should not be read as the trial’s design or as evidence that the study had a particular power. The registry record does not report a sample-size justification or the statistical plan on which enrollment was based. Any planning output is an illustration, not observed power and not a result of the trial.

Recalculated estimates, if presented, are unadjusted calculations from posted summary statistics and should be distinguished from the sponsor’s analysis. The registry record does not report a sponsor analysis for the listed outcomes, and no recalculated comparative result is established by the registry entries. Statistical methods cannot recover unreported participant-level data, endpoint details, or a control comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures, including the primary adverse-event outcome and secondary laboratory, antibody, concentration, and bleeding outcomes. When a study assesses multiple outcomes, there can be more than one opportunity to observe an apparently notable result. General: multiplicity methods can adjust interpretation or testing when several hypotheses are assessed, but their use depends on a prespecified analysis plan and the intended family of outcomes.

Multiplicity procedures or a hierarchy among outcomes are not reported in the registry record. The record also lists 0 analyses, so there is no reported set of inferential tests from which to assess whether or how multiplicity was addressed. The listed outcomes alone do not show that all were analyzed or that any result met a prespecified criterion.

The analysis population is described for safety: it included all participants who received a dose of Factor XIII Concentrate (Human). The record does not report a separate efficacy analysis population, participant flow through outcome assessments, or the handling of missing measurements. Missing-data methods and the extent of missing data are not reported in the registry record. For outcomes measured over follow-up, missing assessments or different observation times can affect what is observed; without details, their influence cannot be evaluated.

The primary endpoint includes events with missing relationship in the treatment-related definition, but that is not a general missing-data method. It does not explain how absent endpoint information or incomplete follow-up was handled. The registry also does not report interim analyses, stopping rules, or a complete statistical analysis plan. These omissions limit assessment of prespecification, multiplicity, and the potential consequences of missing information.

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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: factor xiii inhibition (1.6%), pelvic inflammatory disease (1.6%), pyelonephritis (1.6%), fever (1.6%).

The registry’s safety summary lists 61 participants at risk in the FXIII group, with 2 participants in the serious adverse-event count and 19 in the other adverse-event count. These are separate reported counts. The record does not establish whether the categories overlap, so they should not be added or treated as mutually exclusive groups. The primary endpoint definition covers treatment-emergent, treatment-related, and serious events; the safety summary does not supply enough detail to reconstruct every category’s relationship to that endpoint.

The serious-event terms listed are Factor XIII inhibition, pelvic inflammatory disease, pyelonephritis, and fever, each with a reported value of 1.6%. The registry’s terms and percentages are descriptive entries. They do not establish that an event was caused by treatment, and the record does not give event-level timing or clinical detail. The percentage values should be read as reported rather than used to infer additional counts.

General: a serious adverse event classification concerns the seriousness criteria applied in a study and is distinct from whether an event is judged treatment-related. A descriptive count also does not account for differences in observation time or provide a comparison with an untreated group. The study had no randomized comparator, and no uncertainty estimates for these counts are reported. The figures therefore summarize observed safety reporting in the study group; they do not establish comparative risk or causality.

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

The result is a descriptive safety record from participants who received human Factor XIII concentrate in a prospective, open-enrollment study. The registry reports 2 participants in the serious adverse-event count and 19 in the other adverse-event count, with 61 listed at risk in the group. The serious-event terms and their reported percentages add context to the categories recorded, but they do not identify a treatment effect.

These data do not show what would have happened to comparable participants without the intervention. Because the design was single-group and allocation was not applicable, there is no randomized control contrast. Nor do the counts by themselves establish that treatment caused or prevented any particular event. Attribution of treatment relationship involved investigator judgment, and events with missing relationship were included in the treatment-related definition.

The registry record also does not report uncertainty intervals, statistical tests, adjusted estimates, or a complete analysis plan. The safety counts therefore cannot be treated as precise comparative estimates. The record’s secondary outcome list includes bleeding measures, laboratory testing, antibody testing, and Factor XIII concentration, but their results are not reported in the registry record in the registry entries. The adverse-event counts cannot substitute for those outcome results or answer questions about bleeding outcomes.

The study’s stated context was to provide Factor XIII concentrate to participants until the product became commercially available in the United States. That context helps explain the open-enrollment design, but it does not change the statistical limits of a single-group safety summary. The posted data show events recorded under the study’s definitions and follow-up conditions; they do not establish efficacy, comparative safety, or the absence of unreported events.

Any planning illustration based on a hypothetical two-arm comparison has a separate purpose from the observed study results. Such calculations describe sample sizes under stated assumptions; they are not evidence of the number of participants needed for the actual single-group study, and they are not observed power. The registry record does not report the study’s own sample-size justification.

13. Why This Trial Matters Statistically

This study illustrates a common statistical distinction: collecting safety outcomes in a treated group is not the same as estimating a comparative treatment effect. The registry gives a defined primary safety endpoint, a safety population, and participant counts, so readers can describe what was recorded. But the single-group design provides no concurrent randomized control against which to compare those observations.

That distinction matters especially when interpreting adverse events. Counts can identify that events were recorded and indicate their reported categories, but they cannot establish causality. Treatment-related attribution is a judgment, and open-label status means masking was not used. In addition, participant counts do not describe event timing, recurrence, or individual follow-up in detail. Statistical interpretation must reflect those limits rather than treating a descriptive safety summary as a causal estimate.

The registry’s outcome list also demonstrates why outcome names and outcome results must be separated. Bleeding outcomes, laboratory tests, antibody testing, and Factor XIII concentration are listed, but their results are not reported in the registry record in the registry entries. A list of intended assessments does not establish what those assessments found.

Finally, sample-size planning and observed study evidence answer different questions. A hypothetical two-arm calculation under stated assumptions is not an account of the single-group trial’s statistical design, and it is not observed power. The record does not report its sample-size justification or full analysis plan. These distinctions are central to judging what can be learned from the posted results: descriptive safety information is available, while comparative efficacy and statistical precision are not established by the registry record.

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 principal limitation is the absence of a comparator group. The registry lists a single-group model and allocation as not applicable, so the adverse-event counts cannot be interpreted as a randomized treatment-versus-control contrast. Open-label status and the use of investigator judgment for treatment-related attribution are also relevant when interpreting event classification.

The available safety summary is limited to participant counts and a list of serious-event terms with reported percentages. It does not provide event-level descriptions, timing, recurrence, duration, or individual follow-up. The record does not report confidence intervals, hypothesis tests, adjusted analyses, or detailed results for the listed secondary outcomes. It therefore does not establish the precision of the safety counts or the results of the bleeding, laboratory, antibody, and concentration assessments.

The registry record does not report a full statistical analysis plan, sample-size justification, interim analyses, or stopping rules. It also does not describe missing-data methods or the extent of missing outcome information. Although the safety population is defined as participants who received a dose, further participant flow and outcome-specific analysis populations are not reported.

Follow-up was described as continuing after the first infusion until study completion, up to 2 years or until commercial availability in the USA. The distribution of follow-up time and treatment exposure across participants is not reported. This limits assessment of how opportunity for event recording may have varied. The listed planning framework assumes a hypothetical two-arm comparison, which differs from this single-group study and should not be mistaken for its design or observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open Enrollment Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency — NCT00945906.
• Registry record last updated 2012-10-12; status last verified 2012-09.
• Results first posted 2012-10-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, prospective, multicenter, open-enrollment Phase 3 study of human plasma-derived Factor XIII concentrate in people with congenital Factor XIII deficiency. It lists a single-group model, no masking, enrollment of 61, and treatment by intravenous infusion approximately every 28 days to maintain a trough Factor XIII level of approximately 5 to 20%.

The primary outcome was the number of participants with treatment-emergent, treatment-related, or serious adverse events, assessed after the first infusion through study completion. The safety summary lists 2 participants in the serious-event count and 19 in the other-event count, with 61 at risk. The registry also lists secondary outcomes for laboratory testing, antibodies, Factor XIII concentration, and bleeding, but their results are not reported in the registry record in the registry entries.

No comparator group, statistical analysis, uncertainty interval, full analysis plan, or sample-size justification is reported. The results therefore support a descriptive reading of recorded safety events, not a randomized comparison or a conclusion about treatment effect.