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 Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery (NCT02267226), a na phase 3 study. The primary outcome is Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02267226 |
| Phase | Phase 3 |
| Condition | Congenital Fibrinogen Deficiency |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with congenital fibrinogen deficiency. The registry lists enrollment of 25. Eligibility criteria beyond the condition, participant characteristics, and the number of participants who experienced a documented bleeding episode are not reported in the registry record. The primary endpoint refers to the first documented bleeding episode for each patient, so it is specifically about an episode-based assessment rather than a general measure of bleeding over the entire study.
Intervention
The intervention was Octafibrin, a drug, for on-demand treatment of acute bleeding. The study also included assessment of Octafibrin for preventing bleeding during and after surgery. The record does not report dosing details or describe how treatment decisions were made. The primary endpoint focused on the first documented bleeding episode of each patient, with assessment extending through 24 hours after the last infusion for that episode.
Comparator
There was no comparator group: the registry describes an uncontrolled, single-group study, with allocation listed as not applicable and no masking. Consequently, the record does not support a direct comparison with placebo, another treatment, or untreated outcomes. Any interpretation of the posted efficacy assessment must take account of this design; a clinical assessment made within a treated group is not the same as an estimate of how outcomes differ between treatments.
Primary question
The primary question was how investigators assessed Octafibrin’s haemostatic efficacy in treating the first documented bleeding episode of each patient. The assessment used a 4 point haemostatic efficacy scale, and the final efficacy assessment for each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee. The actual primary endpoint result, including the number of participants in each assessment category or any stated success threshold, is not reported in the registry record. The study also listed outcomes related to clot firmness, plasma fibrinogen level, recovery, all bleeding episodes, and bleeding around surgery.
3. Trial Design
This was a prospective, open-label, uncontrolled, single-group Phase III study of Octafibrin in subjects with congenital fibrinogen deficiency. The registry lists enrollment of 25 and identifies Octapharma as the sponsor. The study started in 2014-09, reached primary completion on 2018-02-14, and is listed as completed. Allocation was not applicable, and masking was none. These features mean that the study did not use a randomized or masked comparison between treatment groups.
The stated purpose was to assess Octafibrin for on-demand treatment of acute bleeding. The title and secondary outcomes also include prevention of bleeding during and after surgery. The primary endpoint was the overall clinical assessment of haemostatic efficacy for the first documented bleeding episode of each patient. The assessment period ran from the first Octafibrin infusion until 24 hours after the last infusion for the episode. An investigator made the assessment using a 4 point scale, and an independent committee adjudicated the final assessment.
The record does not report the protocol’s eligibility details, dosing schedule, criteria for initiating treatment, or the criteria used to classify a haemostatic response. It also does not report a sample-size justification or a detailed statistical analysis plan. Without a comparator group, the design can describe outcomes observed during treatment but cannot by itself separate treatment effects from other explanations for those outcomes.
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 | Octafibrin |
|---|---|
| STARTED | 25 |
| SAFETY Population | 25 |
| FAS-Bleeding Population | 24 |
| Surgical Prophylaxis Population | 9 |
| COMPLETED | 18 |
| NOT COMPLETED | 7 |
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.
Population: All patients who received at least one Octafibrin administration during the study.
| Characteristic | Unit | SAFETY Population |
|---|---|---|
| Participants analysed | 25 | |
| Age, Categorical: <=18 years | Participants | 6 |
| Age, Categorical: Between 18 and 65 years | Participants | 19 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 29.04 (SD 12.95) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 14 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 19 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient., measured over 24 hours after last infusion for each bleeding episode.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the overall clinical assessment of Octafibrin’s haemostatic efficacy in treating the first documented bleeding episode of each patient. It was expressed in participants, and the assessment used a 4 point haemostatic efficacy scale. The episode covered the period from the first Octafibrin infusion through 24 hours after the last infusion. The investigator assessed efficacy, and the final assessment for each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee.
A clinical haemostatic assessment is intended to capture whether bleeding is judged to be controlled in the clinical setting, rather than relying only on a laboratory measurement. That is a general explanation of this type of endpoint; the registry record does not describe the scale’s category definitions, the threshold for classifying an outcome as successful, or how an assessment was handled when evidence was incomplete. Those details matter because different thresholds can produce different summaries of the same underlying assessments.
The endpoint is relevant to the study’s acute-bleeding objective, but its result is not reported in the registry record. The record therefore does not permit readers to assess the distribution of clinical ratings or the precision of an estimated response proportion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clinical efficacy endpoint, but does not report its result. It gives no count or proportion of participants in the haemostatic efficacy categories, no estimated response proportion, and no confidence interval for the primary endpoint. A numerical efficacy conclusion cannot be drawn from the endpoint description alone. The record also does not state a threshold that would define a favourable response, so a reader cannot reconstruct such a classification from the scale description.
The study was uncontrolled and open-label. In general, an uncontrolled study can document what was observed among treated participants, but it cannot establish how those outcomes compare with what would have happened under another treatment or without treatment. Open-label assessment may also be influenced by knowledge of treatment, although adjudication by an independent committee provides an additional review process. The registry record does not describe the committee’s procedures or how disagreements were resolved.
The primary endpoint concerns the first documented bleeding episode for each patient, while secondary outcomes include all bleeding episodes and outcomes related to surgery and laboratory measures. These address different questions and should not be treated as interchangeable evidence. The record lists the secondary outcomes but does not provide their results. It also does not report statistical analyses in the registry record, so there are no posted effect estimates, uncertainty intervals, or hypothesis tests to interpret for these outcomes.
The enrollment figure and the safety counts describe the study’s scale and safety reporting, not the missing primary efficacy result. Safety findings cannot substitute for an efficacy estimate. In particular, the adverse-event summaries do not show whether bleeding was controlled under the primary assessment, nor do they provide a comparative safety estimate. The registry record therefore supports a description of the design, endpoint, and listed safety events, but not a quantitative conclusion about efficacy or a comparative treatment effect.
9. Statistical Methods Explained
The registry describes a single-group study and identifies the primary outcome as a participant count based on a clinical assessment. These registry entries define the broad statistical setting, but the record does not give a detailed analysis plan. It does not report the statistical model, the treatment of incomplete assessments, a confidence-interval method, or a hypothesis test for the primary endpoint. The absence of those details limits the ability to reproduce or fully evaluate an analysis from the registry record.
What does a participant count represent?
A count describes how many participants meet a stated classification or experience an event. For an efficacy scale, interpretation depends on the category definitions and on whether the analysis reports each category separately or combines categories into a response definition. The registry identifies a 4 point haemostatic efficacy scale but does not report its category labels or a threshold for combining them. It also does not report the primary endpoint count. No response proportion or other derived efficacy statistic can therefore be interpreted from the registry record.
In general, a confidence interval conveys the uncertainty around an estimate and gives a range of values compatible with the data under the chosen statistical method. Its width depends on factors including the amount of information and the variability in the data. A point estimate without an interval can make a result appear more precise than the data justify. For this trial, no primary endpoint estimate or confidence interval is reported in the registry record, so its precision cannot be assessed.
Why does the study design matter?
In a single-group study, outcomes are observed among participants receiving the study intervention. Without a concurrent comparator, statistical analysis cannot directly estimate a difference between Octafibrin and another treatment. A before-and-after comparison or a comparison with an external expectation would require suitable data and assumptions; neither is described in the registry record. Statistical adjustment cannot create a randomized comparator where none exists.
Open-label conduct means the treatment was not masked. For a clinical rating, knowledge of treatment can be relevant to assessment. Independent adjudication is reported for the final efficacy assessment, which provides a separate review of the investigator’s assessment. The record does not explain how information was presented to the adjudication committee or whether it was masked to other details. These missing procedural details make it difficult to judge how much the adjudication process could reduce potential assessment bias.
What can the planning assumptions tell readers?
The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are assumptions for a planning calculation, not a description of the trial’s single-group design. Any resulting sample-size estimate is an illustration and not observed power. The registry record does not report the trial’s own sample-size justification, and the primary endpoint result needed to interpret an observed-effect-based illustration is not reported in the registry record.
In general, a sample-size calculation depends on the target effect, variability, statistical test, allocation, and chosen error rates. Changing an assumption changes the planning estimate. A calculation based on an observed effect should not be read as proof that the trial had adequate power: observed effects can be imprecise, especially when the underlying dataset is limited. No calculated sample-size values are described in the registry record’s trial design information, and the planning assumptions do not replace a prospective justification.
How should multiple outcomes be considered?
The record lists the primary endpoint alongside secondary outcomes concerning maximum clot firmness, plasma fibrinogen level, incremental in vivo recovery, all bleeding episodes, and bleeding during and after surgery. These measures may address related but distinct clinical or laboratory questions. When several outcomes are assessed, multiplicity can arise if many statistical tests are used to support claims. In general, multiplicity procedures can control the chance of false-positive findings across a defined family of tests, but the registry record does not report whether such procedures were planned or used. Since no analyses are listed in the registry record, there are no posted tests to evaluate for multiplicity.
The registry also does not report a missing-data method, an analysis population for the primary endpoint, or how participants without an eligible bleeding episode or a complete assessment were handled. These details affect the denominator and the interpretation of a participant count. The safety summary names a safety population, but that does not establish the analysis population used for efficacy. As a result, readers cannot determine from the registry record whether the primary endpoint analysis included all enrolled participants or a defined subset.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures and identifies one primary endpoint, with secondary outcomes covering laboratory measures, recovery, all bleeding episodes, and prevention of bleeding during and after surgery. The record lists no analyses. It does not report whether statistical testing was planned for the secondary outcomes, whether any multiplicity adjustment was used, or which outcomes would be treated as confirmatory. In general, testing many outcomes can increase the chance that an apparently notable result occurs by chance; the registry record does not provide enough information to assess that issue for this study.
Missing-data methods for the primary or secondary outcomes are not reported in the registry record. The record does not describe how participants with no documented bleeding episode, incomplete clinical assessments, or unavailable laboratory measurements were handled. It also does not report a primary efficacy analysis population. The endpoint is defined in terms of the first documented bleeding episode of each patient, but the record does not state how participants without such an episode would enter an efficacy summary.
A safety population is identified for adverse-event reporting. That label should not be assumed to define the efficacy analysis population. The registry does not report whether all enrolled participants were included in each analysis or how the denominators for the outcome measures were determined. These omissions limit assessment of potential selection effects and make it difficult to reproduce the analyses.
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 |
|---|---|---|---|
| Safety Population | 5 | 25 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Safety Population | 0 of 25 |
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 |
|---|---|
| Safety Population | 19 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 25 |
| Ligament rupture | Injury, poisoning and procedural complications | 1 of 25 |
| Ligament sprain | Injury, poisoning and procedural complications | 1 of 25 |
| Patella fracture | Injury, poisoning and procedural complications | 1 of 25 |
| Transfusion reaction | Injury, poisoning and procedural complications | 1 of 25 |
| Accelerated hypertension | Vascular disorders | 1 of 25 |
| Thrombosis | Vascular disorders | 1 of 25 |
| Peripheral ischaemia | Vascular disorders | 1 of 25 |
| Dengue fever | Infections and infestations | 1 of 25 |
| Hepatitis C | Infections and infestations | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Limb injury | Injury, poisoning and procedural complications | 3 of 25 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 3 of 25 |
| Gingival bleeding | Gastrointestinal disorders | 2 of 25 |
| Vomiting | Gastrointestinal disorders | 2 of 25 |
| Hypertension | Vascular disorders | 2 of 25 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 25 |
| Ecchymosis | Skin and subcutaneous tissue disorders | 2 of 25 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 25 |
| Constipation | Gastrointestinal disorders | 1 of 25 |
| Gastritis | Gastrointestinal disorders | 1 of 25 |
Serious events with the highest arm-level rate: upper gastrointestinal haemorrhage (4.0%), ligament rupture (4.0%), ligament sprain (4.0%), patella fracture (4.0%), transfusion reaction (4.0%).
The safety summary identifies a Safety Population of 25. It reports 5 participants with serious adverse events, 19 with other adverse events, and 0 deaths. These are participant counts as reported in the registry record; they are not efficacy results. The record does not provide a comparative group, so the figures do not estimate how safety outcomes differ from those under another treatment.
The registry lists Upper gastrointestinal haemorrhage, Ligament rupture, Ligament sprain, Patella fracture, Transfusion reaction, and Accelerated hypertension among the serious adverse event terms, each at 4.0%. These term percentages should not be added together to infer a total number of affected participants. The record does not say whether a participant could contribute to more than one term, and the terms do not necessarily represent separate individuals.
The registry record does not report whether investigators considered the events related to Octafibrin, how event seriousness was defined, or the timing and duration of the events. The counts describe what was recorded in the safety summary, but they do not by themselves establish causation or provide a comparison with another treatment.
12. What the Result Does, and Does Not, Mean
The study record establishes that Octafibrin was evaluated in a prospective, open-label, uncontrolled Phase III study among subjects with congenital fibrinogen deficiency. It identifies a clinically assessed primary endpoint focused on the first documented bleeding episode and lists laboratory, repeated-episode, and surgical outcomes. These details clarify the study’s question and the types of outcomes considered.
The primary efficacy result is not reported in the registry record. Without a reported assessment count, response definition, or estimate with uncertainty, readers cannot determine the observed efficacy distribution or its precision. The listed safety counts provide a limited description of recorded events, but they do not answer the primary efficacy question. The registry record also does not provide a controlled comparison, so it cannot show how outcomes differ from another treatment or from no study intervention.
In general, evidence from an uncontrolled study is best interpreted as a description of outcomes in the treated group, rather than as a definitive estimate of comparative treatment effect. Clinical assessment and adjudication are relevant features of the endpoint process, but they do not substitute for reporting the result and its uncertainty. Likewise, the presence of secondary laboratory or clinical outcomes in a registry does not establish what those outcomes showed when their results are not reported.
The record supports statements about the design, planned outcome domains, enrollment, and safety summary. It does not support a conclusion that Octafibrin does or does not control bleeding, prevent surgical bleeding, or cause any listed event. Those conclusions would require reported outcome data and, for comparative claims, an appropriate comparison.
13. Why This Trial Matters Statistically
This study raises statistical issues that are important when a rare condition is examined in a single-group clinical study. The registry identifies congenital fibrinogen deficiency as the condition and lists enrollment of 25. In this setting, clear outcome definitions and transparent reporting are particularly important: readers need to know what counts as a favourable haemostatic assessment, which participants contribute to the analysis, and how uncertainty around the result is represented. The registry record does not report the primary endpoint result or these analysis details.
The endpoint combines clinical judgment with independent adjudication. That approach makes the assessment process central to interpretation. Reporting the scale categories, the decision rules, and the adjudication procedures would help readers understand how clinical observations became the final endpoint classification. The registry record confirms use of a 4 point scale and independent committee adjudication, but does not give those further details.
The uncontrolled design also illustrates a distinction between describing outcomes and estimating comparative effects. A single-group study can document events and assessments among treated participants, while a treatment comparison requires a suitable comparator and a defined analysis. The record does not include a control group or posted efficacy analyses. Its value for statistical interpretation therefore depends on careful recognition of what the design and available reporting can establish, and what they cannot.
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 primary endpoint result is not reported in the registry record. There is no reported distribution across the haemostatic efficacy scale, response threshold, effect estimate, or confidence interval. This prevents assessment of the observed primary outcome and its precision.
The study was open-label, uncontrolled, and single-group, with allocation listed as not applicable and masking listed as none. No comparator is available for estimating a treatment difference. The registry does not report details of the endpoint category definitions, the adjudication process beyond committee review, or criteria for classifying a response.
The record does not report a detailed statistical analysis plan, missing-data procedures, the primary efficacy analysis population, or a sample-size justification. Although it lists secondary outcomes, their results and any multiplicity procedures are not reported. It also does not describe dosing, eligibility details, or how participants without a documented bleeding episode were handled in the primary endpoint analysis.
The safety summary gives participant counts and serious adverse event terms, but does not report event attribution, timing, or whether participants contributed to multiple terms. These limitations constrain interpretation of both efficacy and safety. They are limitations of what the registry record reports and do not establish what may have been described elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery — NCT02267226.
- Registry record last updated 2021-01-15; status last verified 2020-12.
- Results first posted 2019-02-20.
- 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.
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18. Record Summary
NCT02267226 is a completed, prospective, open-label, uncontrolled, single-group Phase III study sponsored by Octapharma. It evaluated Octafibrin for on-demand treatment of acute bleeding in subjects with congenital fibrinogen deficiency and also included outcomes concerning bleeding during and after surgery. The registry lists enrollment of 25.
The primary endpoint was an investigator’s overall clinical assessment of haemostatic efficacy for the first documented bleeding episode of each patient, using a 4 point scale. The final assessment was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee. The primary endpoint result and statistical analyses are not reported in the registry record. The safety summary reports 5 participants with serious adverse events, 19 with other adverse events, and 0 deaths.