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 Immunogenicity and Safety Study of rThrombin in Surgical Hemostasis (NCT00813904), a na phase 4 study. The primary outcome is Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00813904 |
| Phase | Phase 4 |
| Condition | Blood Loss, Surgical |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ZymoGenetics |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with prior exposure to rThrombin who received study treatment. For the primary antibody assessment, the stated population was participants with data available from both baseline and Day 29 assessments. The registry record lists enrollment of 31 participants; it does not report how many had complete data for both antibody assessments.
Intervention
The intervention was rThrombin at 1000 IU/mL, used in the context of surgical hemostasis. The study objective was to assess immunogenicity and safety following re-exposure. The registry record describes the study as open-label, so treatment masking was absent.
Comparator
There was no comparator group. The design is listed as single-group, with allocation recorded as not applicable. Consequently, the study does not provide a randomized, concurrent comparison with another treatment or with no treatment.
Primary question
The primary question was whether antirThrombin product antibodies were detected at baseline and Day 29 among the participants with both assessments available. The evaluation used an enzyme-linked immunosorbent assay to detect product antibodies and a neutralizing antibody assay to characterize their potential to neutralize human plasma-derived thrombin activity. The registry record does not report the antibody counts or a comparison between assessment times.
3. Trial Design
This was a Phase 4, open-label, single-group immunogenicity and safety study of re-exposure to rThrombin in surgical hemostasis. The registry record lists 31 participants enrolled and the study status as completed. It identifies blood loss during surgery as the condition and ZymoGenetics as the sponsor. The recorded start was 2009-01, and primary completion was 2010-07.
All participants were assigned to the single intervention, rThrombin at 1000 IU/mL. Allocation is recorded as not applicable, and masking as none. These features describe a study intended to observe antibody and safety outcomes in participants receiving treatment, rather than to estimate a randomized treatment contrast. No control arm or alternative treatment group is listed.
The stated objective focused on patients with prior rThrombin exposure. The primary endpoint concerned antibodies at baseline and Day 29, while the listed secondary outcomes concerned deaths, serious adverse events, treatment-related serious adverse events, adverse events, treatment-related adverse events, discontinuations due to adverse events, and adverse events by maximum severity. The registry record lists three outcome measures, but does not include the results for the primary antibody outcome.
The design sets important boundaries on interpretation. In a single-group study, an observed outcome describes participants in that group; it does not by itself establish how the outcome would compare under another treatment or without treatment. The open-label status also means masking cannot be assumed for treatment administration or outcome assessment. The registry record does not report additional design details, such as eligibility criteria, the exact treatment schedule, or the protocol’s rationale for the enrollment target.
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 31 participants enrolled, all received treatment with recombinant thrombin (rThrombin).
Overall Study
| Stage | rThrombin, 1000 IU/mL |
|---|---|
| STARTED | 31 |
| COMPLETED | 30 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | rThrombin, 1000 IU/mL |
|---|---|
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants who received treatment with rThrombin and had data available from both baseline and Day 29 antibody assessments.
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 | rThrombin, 1000 IU/mL |
|---|---|---|
| Participants analysed | 31 | |
| Age, Customized | Years | 59.5 (SD 12.3) |
| Age, Customized: Median | Years | 61.0 (22.0 to 81.0) |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 19 |
| Type of surgery: Arterial reconstruction/peripheral arterial bypass | Participants | 4 |
| Type of surgery: Arteriovenous vascular access procedure | Participants | 3 |
| Type of surgery: Other | Participants | 1 |
| Type of surgery: Spinal | Participants | 23 |
6. Primary Endpoint
The registry lists the primary outcome as Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29, measured over At baseline and Day 29.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a participant count: the number of participants with antirThrombin product antibody at baseline and Day 29. It addresses immunogenicity, meaning the development or presence of an antibody response directed against the administered product. The registry description specifies an enzyme-linked immunosorbent assay for detecting product antibodies and a neutralizing antibody assay to characterize whether antibodies could neutralize the activity of human plasma-derived thrombin.
Assessing antibody status at both time points is relevant to a re-exposure study because the question concerns immune findings before and after treatment. However, the registry record does not report the observed counts at either time point, the number of participants with paired assessments, or how the results were classified for analysis. It therefore does not establish from the posted results whether antibody findings changed between baseline and Day 29.
A participant count is readily interpretable as the number meeting a defined outcome, but it does not describe the strength of an antibody response unless additional measurements are reported. Nor does a count alone show whether an antibody neutralized thrombin activity. The assays are described, but assay thresholds, quantitative antibody values, and the endpoint’s detailed decision rules are not reported in the registry record. These details matter when interpreting what a positive result represents and how comparable results would be across studies.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study objective, design, endpoint, and some safety counts, but it does not report the primary antibody results. The endpoint title specifies antibody assessments at baseline and Day 29, yet the number of participants with antibodies at either assessment is not reported in the registry record. The number with data available from both assessments is also not reported. Therefore, the primary immunogenicity outcome cannot be described quantitatively from this record.
The study is single-group and open-label. Its observations can describe the participants who received rThrombin, but there is no concurrent comparator to distinguish an outcome associated with treatment from an outcome that might have occurred for other reasons. The record does not support a treatment-versus-control estimate, and it does not provide a randomized comparison. That limitation is separate from whether an antibody finding was observed: even a complete antibody count would remain a descriptive result in this design.
The safety information includes a reported count of 6 participants with serious adverse events among 31 at risk and 29 participants with other adverse events among 31 at risk. These figures describe reported participant counts, not a causal treatment effect. The registry record does not provide the event-level context needed to attribute each event to treatment. Although treatment-related events are among the listed outcomes, their corresponding results are not reported in the registry record. The record also does not report a death count; a missing count should not be interpreted as a count of zero.
The listed serious-event terms each have a posted value of 3.2%. Those entries identify reported terms and percentages, but the registry record does not give accompanying event counts or enough detail to establish a causal relationship. They should not be read as evidence that rThrombin caused those events. The record also does not report the timing, duration, or clinical circumstances of the events in a way that would support a more detailed interpretation.
No confidence intervals, p-values, or inferential analysis results are reported in the registry record. Thus, the precision of the antibody estimate cannot be assessed, and there is no reported statistical test of change between baseline and Day 29. The posted information is best read as a limited descriptive account: a completed single-group study with specified antibody assays and reported safety counts, but without the primary antibody outcome results or a comparative analysis.
9. Statistical Methods Explained
What does the endpoint count?
The primary endpoint is expressed as a number of participants with antirThrombin product antibody at baseline and Day 29. This is a participant-level outcome: a person is classified according to whether the antibody finding meets the study’s criteria. The endpoint is not an event rate over person-time, and it is not a continuous measurement of antibody concentration as described in the registry record. The record identifies the assays but does not report the classification thresholds or the resulting counts.
For a binary participant outcome, a useful descriptive presentation commonly includes the number meeting the definition and the number assessed at each time point. When the same participants are measured at more than one time, paired information can also be useful, because the baseline and later observations are linked within participants. The registry record does not report these counts or a paired analysis. This general description explains how such outcomes can be summarized; it does not imply that any particular analysis was performed in this study.
How should a confidence interval be understood?
In general, a confidence interval describes the uncertainty around an estimate under a statistical model and its assumptions. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. For a participant count or proportion, uncertainty depends in part on how many participants were assessed and how frequently the outcome occurred. The registry record does not report an interval for the antibody outcome or a numerical estimate from which its precision could be judged.
A confidence interval is not a guarantee that the true value lies within its limits, and it does not replace consideration of study design. In a single-group study, an interval around an observed outcome would quantify uncertainty about that group’s result; it would not create a comparison group or establish what would have happened under another treatment. No confidence interval estimates are reported in the registry record.
What can a single-group design estimate?
A single-group study can describe what was observed among the participants studied. It cannot, by design alone, separate the effect of treatment from other influences such as the underlying condition, procedures, concurrent care, or changes over time. A baseline measurement can provide context for a later measurement, but baseline is not a randomized control group. Any comparison between baseline and Day 29 would require an appropriate analysis of paired data and careful interpretation; the registry record does not report such an analysis.
Open-label status is another design feature to keep in view. With no masking, knowledge of treatment assignment may influence some aspects of care, event reporting, or assessment. This does not establish that bias occurred. It means that readers cannot assume masking protected the study from those possible influences. The registry record does not describe additional steps used to reduce assessment bias.
How do the planning assumptions differ from the trial design?
The planning illustration is described as a calculation based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers detection of a stated fraction of the observed effect. These are planning assumptions, not a description of this trial’s single-group design. The illustration is not observed power and does not show the probability that this completed study detected an effect.
The stated planning approach distinguishes between participant-per-arm calculations for most outcomes and total event calculations for time-to-event outcomes using the Schoenfeld method. Those general conventions do not change the actual design recorded for this study: it has a single group and no comparator. The registry record does not report numerical planning results, the effect estimate used for those calculations, or a sample-size justification for the trial itself. No planning figure should be interpreted as a count of participants actually observed in a comparison or as evidence that the study was adequately powered.
What is not established by the analysis record?
The registry record lists zero analyses. This does not establish that no statistical work was ever undertaken; it indicates that analysis results are not posted in the registry record. It reports no model, hypothesis test, confidence interval, adjustment for covariates, or estimate comparing time points. Readers therefore should not infer a particular statistical procedure from the fact that the endpoint is a participant count.
In general, count outcomes can be analyzed in different ways depending on the question, data structure, and assumptions. For a simple binary outcome, the event count and assessed population are central descriptive quantities. For repeated measurements on the same participants, methods should account for that within-participant relationship if an inferential comparison is intended. For count data with variability greater than a model assumes, over-dispersion can make standard errors too small if ignored; this general concern is relevant only when an appropriate count model is being used. The registry record does not report that such a model, or any other model, was used.
Because the primary result and analysis details are absent, neither statistical significance nor precision can be assessed for immunogenicity. The defensible statistical reading is limited to the documented design, endpoint definition, assay descriptions, and reported safety counts. Further conclusions would require results and methods that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures and names secondary safety outcomes covering deaths, serious adverse events, treatment-related serious adverse events, adverse events, treatment-related adverse events, discontinuations due to adverse events, and adverse events by maximum severity. It does not report a plan for controlling multiplicity across outcomes, time points, or antibody assays. The absence of a reported plan does not establish that no plan existed; it means that multiplicity procedures are not reported in the registry record.
Multiplicity matters when several outcomes or comparisons are examined because the chance of at least one apparently notable result can increase as more tests are considered. In general, an analysis plan may specify a primary endpoint, testing hierarchy, or adjustment method to guide interpretation. The endpoint is identified as primary in the record, but no statistical testing hierarchy or adjustment is described. No p-values are reported, so the effect of any multiplicity procedure cannot be assessed.
The primary population is defined as participants who received rThrombin and had both baseline and Day 29 antibody assessments available. The record does not state how many participants met that definition or whether missing antibody measurements were handled by exclusion, imputation, or another approach. Missing-data methods are not reported in the registry record. The reasons for unavailable assessments and the timing of any withdrawals are also not reported.
The registry record does not describe an analysis population for the safety outcomes beyond the reported at-risk counts. It does not specify a per-protocol or intention-to-treat population, nor does it describe sensitivity analyses. These omissions limit assessment of how participants with incomplete data or protocol deviations were treated. The posted information supports neither an assumption that data were complete nor an assumption about how missing observations affected the results.
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 |
|---|---|---|---|
| TOTAL | 6 | 31 | 19.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| TOTAL | 29 of 31 |
Most frequent serious adverse event terms
| Event term | Organ system | TOTAL |
|---|---|---|
| CHEST PAIN | General disorders | 1 of 31 |
| OSTEOMYELITIS | Infections and infestations | 1 of 31 |
| SEPSIS | Infections and infestations | 1 of 31 |
| OVERDOSE | Injury, poisoning and procedural complications | 1 of 31 |
| PROCEDURAL HYPOTENSION | Injury, poisoning and procedural complications | 1 of 31 |
| SYNCOPE | Nervous system disorders | 1 of 31 |
| RENAL FAILURE | Renal and urinary disorders | 1 of 31 |
| RENAL FAILURE CHRONIC | Renal and urinary disorders | 1 of 31 |
| ARTERIAL THROMBOSIS LIMB | Vascular disorders | 1 of 31 |
| HYPOTENSION | Vascular disorders | 1 of 31 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TOTAL |
|---|---|---|
| PROCEDURAL PAIN | Injury, poisoning and procedural complications | 23 of 31 |
| CONSTIPATION | Gastrointestinal disorders | 8 of 31 |
| NAUSEA | Gastrointestinal disorders | 8 of 31 |
| TACHYCARDIA | Cardiac disorders | 6 of 31 |
| ANAEMIA POSTOPERATIVE | Injury, poisoning and procedural complications | 6 of 31 |
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | 6 of 31 |
| INCISION SITE PAIN | Injury, poisoning and procedural complications | 5 of 31 |
| INSOMNIA | Psychiatric disorders | 4 of 31 |
| PRURITUS | Skin and subcutaneous tissue disorders | 4 of 31 |
| PYREXIA | General disorders | 3 of 31 |
Serious events with the highest arm-level rate: chest pain (3.2%), osteomyelitis (3.2%), sepsis (3.2%), overdose (3.2%), procedural hypotension (3.2%).
The registry record reports 6 participants with serious adverse events among 31 at risk and 29 participants with other adverse events among 31 at risk. These are participant counts. They are not comparisons between treatment groups, because the study has no comparator, and they do not by themselves establish that treatment caused an event.
The listed serious-event terms are chest pain, osteomyelitis, sepsis, overdose, procedural hypotension, and syncope, each with a posted value of 3.2%. The record does not provide event counts alongside those terms or describe enough context to determine attribution. These percentages should be read as registry-listed term values, not as proof of treatment causation or as a complete account of clinical seriousness.
Death, treatment-related serious events, treatment-related adverse events, and adverse events leading to discontinuation are among the stated safety outcomes, but their results are not reported in the registry record. In particular, the death count is not reported; it should not be interpreted as zero. The record does not describe event timing, duration, recurrence, or participant-level overlap between categories. These safety figures are therefore descriptive and incomplete for judging comparative risk.
12. What the Result Does, and Does Not, Mean
This study addresses a focused question about immunogenicity and safety after rThrombin re-exposure in patients with prior exposure. Its primary endpoint is based on antibody detection at baseline and Day 29, using assays intended to detect product antibodies and characterize neutralizing potential. The design and endpoint are documented, but the primary antibody counts are not reported in the registry record. As a result, the posted record does not show how many participants had antibodies at either assessment or whether results differed over time.
The safety results that are posted describe participant counts in the single treatment group. They are not evidence from a randomized comparison and do not isolate the contribution of treatment from other possible causes. The listed serious-event terms and percentages also do not, by themselves, demonstrate that rThrombin caused the events. The missing results for treatment-related events and deaths prevent a complete reading of the listed safety outcomes.
In general, a finding of antibodies and a finding of neutralizing activity are not interchangeable. Detection of an antibody does not alone establish that it neutralizes thrombin activity, and the registry description identifies a separate assay for that potential. Since assay results and decision thresholds are not reported, the biological meaning of any specific participant-level result cannot be evaluated from the record.
The record also does not report confidence intervals or inferential tests. The precision and statistical uncertainty of the antibody outcome therefore cannot be assessed. Even if the outcome counts were available, the single-group design would support description rather than a controlled estimate of treatment effect. The registry record is informative about the intended assessment and study structure, but it does not establish comparative efficacy, a causal safety effect, or a quantitative change in immunogenicity.
13. Why This Trial Matters Statistically
This trial illustrates why the design and the result must be read together. The stated clinical and statistical focus is antibody response after re-exposure, with assessments at baseline and Day 29. The use of an antibody-detection assay alongside a neutralizing antibody assay reflects two related but distinct questions: whether antibodies are detected, and whether their activity could neutralize human plasma-derived thrombin. Keeping those questions separate is important when interpreting immunogenicity outcomes.
The single-group structure also highlights the difference between describing outcomes and estimating comparative effects. Participant counts can document what was observed among treated participants, but without a comparator they cannot show how those outcomes differ from an alternative treatment or from no treatment. This limitation applies to the primary endpoint and to adverse events alike.
The record further shows why outcome definitions and analysis details matter. Knowing that an endpoint concerns antibody presence at specified assessments is not enough to assess its precision or interpret a change. The assessed population, observed counts, missing-data handling, and any paired analysis would all help readers understand the result. Those details are not reported in the registry record.
Finally, safety counts are most informative when accompanied by event context, attribution, and complete outcome reporting. The available counts describe reported participants with events, but treatment-related results and the death count are not reported. Statistically, the study is therefore a useful example of how a clear objective and assay description can coexist with substantial limits on what can be inferred from posted results.
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 limitation is that the registry record does not report the primary antibody counts at baseline or Day 29, nor the number with both assessments available. The endpoint’s assay methods are described, but thresholds, quantitative measurements, and detailed classification rules are not reported. This prevents evaluation of the magnitude, direction, or precision of the primary outcome.
The single-group, open-label design limits comparative interpretation. There is no randomized control group, so observed antibody or safety findings cannot be contrasted with an alternative treatment group. Open-label status also means that masking cannot be assumed. The record does not describe whether independent or blinded outcome assessment was used.
Safety reporting is incomplete for several outcomes named in the record. The death count and results for treatment-related adverse events, treatment-related serious adverse events, and discontinuations due to adverse events are not reported in the registry record. Event-level details, timing, and participant-level overlap across safety categories are also not reported. The listed serious-event terms and percentages alone cannot establish causality.
Statistical methods are not described in the registry record. It lists zero analyses and does not report confidence intervals, p-values, a model, multiplicity handling, or missing-data methods. The number of participants eligible for the paired primary assessment and the reasons for any unavailable measurements are not reported. The record also does not report eligibility criteria, treatment schedule details, or the trial’s sample-size justification. These gaps limit assessment of precision, analysis populations, and the robustness of any result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity and Safety Study of rThrombin in Surgical Hemostasis — NCT00813904.
- Registry record last updated 2011-12-08; status last verified 2011-11.
- Results first posted 2011-12-08.
- 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.
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18. Record Summary
The registry record describes a completed Phase 4, open-label, single-group study of rThrombin at 1000 IU/mL in surgical hemostasis. It lists enrollment of 31 participants, ZymoGenetics as sponsor, and the study objective of assessing immunogenicity and safety in patients with prior rThrombin exposure.
The primary endpoint concerns the number of participants with antirThrombin product antibody at baseline and Day 29, using an enzyme-linked immunosorbent assay and a neutralizing antibody assay. The antibody outcome counts are not reported in the registry record. Safety results include 6 participants with serious adverse events and 29 with other adverse events among 31 at risk; the death count and several treatment-related outcomes are not reported.
No comparator, analysis results, confidence intervals, p-values, or missing-data methods are reported. The record therefore supports a description of the study design and posted safety counts, but not a comparative treatment estimate or a quantitative interpretation of the primary immunogenicity outcome.