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 C1 Esterase Inhibitor in Hereditary Angioedema (HAE)(Extension Study) (NCT00292981), a non-randomized phase 3 study. The primary outcome is Time to Start of Relief of Symptoms From HAE Attack (Intent to Treat (ITT) Subject Population).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00292981 |
| Phase | Phase 3 |
| Condition | Hereditary Angioedema |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 57 |
| Arms in the primary outcome | n/a |
| Lead sponsor | CSL Behring |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with congenital C1-INH deficiency and acute hereditary angioedema attacks. Its planned participants were subjects who had participated in the pivotal study. The registry record reports enrollment of 57 subjects and identifies hereditary angioedema as the condition. For the primary endpoint, the intent-to-treat subject population is defined as all subjects admitted to the study who received any portion of the study medication. The record does not report further demographic or clinical characteristics of this population.
Intervention
The intervention was C1 Esterase Inhibitor, described in the official title as human pasteurized C1 esterase inhibitor concentrate. The study was intended to provide C1-INH for treatment of acute HAE attacks. The brief summary says the extension was planned to continue for 24 months or until the licensing procedure for C1-INH was finalized, whichever came first. The registry record does not report additional details about administration in the intervention description.
Comparator
There was no concurrent comparator group. The trial is identified as non-randomized, unmasked, and single-group. The record therefore does not describe a randomized contrast between C1 Esterase Inhibitor and placebo, usual care, or another treatment. Results from this study should be understood as observations from the extension cohort, not as a like-for-like comparison with a control arm.
Primary question
The primary endpoint asks how long it took to start relief of symptoms from an HAE attack after study treatment began. Time was measured in hours, and symptom relief was determined by subject self-assessment. The endpoint was specified for the intent-to-treat subject population, with a timeframe of up to 24 h after the start of study treatment. The registry record identifies the planned measure as a median with a 95% confidence interval, but the observed median and interval are not reported in the registry record. The record therefore does not provide the primary result needed to describe the observed timing or its statistical precision.
3. Trial Design
This was a Phase 3, completed extension study of C1 Esterase Inhibitor in hereditary angioedema. The registry identifies it as non-randomized, with no masking and a single-group model. Enrollment was 57. The study started in 2005-08, reached primary completion in 2010-02, and has a completed status. CSL Behring is listed as the sponsor.
The official title describes an open-label extension study of human pasteurized C1 esterase inhibitor concentrate in subjects with congenital C1-INH deficiency and acute HAE attacks. The brief summary says the extension was planned to enroll subjects who participated in the pivotal study, providing C1-INH for acute attacks for 24 months or until the licensing procedure was finalized, whichever came first. These are statements of the planned extension; the registry record does not report further details about how long individual subjects participated or how many attacks were treated.
Because the study had one group and no random allocation, there is no concurrent randomized control against which to estimate a treatment contrast. The open-label design also means there was no masking. Those design features matter when interpreting outcomes based on subject assessment: the reported endpoint depends on a participant's judgment of when relief began, and the record does not describe a blinded assessment process. This does not establish the direction or size of any potential measurement influence; it identifies a consideration when reading the design.
The registry lists four outcome measures, including the primary measure of time to start of relief and secondary measures of time to complete resolution of all HAE symptoms in the ITT subject population and the ITT attack population. It does not report outcome estimates in the record. In particular, the median and 95% confidence interval for the primary endpoint are not reported in the registry record. The design and endpoint definitions can therefore be described, but the primary outcome magnitude cannot be characterized from the posted results.
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 | C1 Esterase Inhibitor |
|---|---|
| STARTED | 57 |
| COMPLETED | 18 |
| NOT COMPLETED | 39 |
Reasons for not completing this period:
| Reason | C1 Esterase Inhibitor |
|---|---|
| Adverse Event | 1 |
| Lost to Follow-up | 13 |
| Withdrawal by Subject | 22 |
| Other | 3 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) subject population: All subjects admitted to the study who received any portion of the study medication.
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 | C1 Esterase Inhibitor |
|---|---|---|
| Participants analysed | 57 | |
| Age, Continuous | years | 31.9 (SD 11.98) |
| Sex: Female, Male: Female | Participants | 38 |
| Sex: Female, Male: Male | Participants | 19 |
| Type of HAE: Type I HAE | participants | 49 |
| Type of HAE: Type II HAE | participants | 7 |
| Type of HAE: Unknown | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Start of Relief of Symptoms From HAE Attack (Intent to Treat (ITT) Subject Population), measured over Up to 24 h after start of study treatment.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | hours |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is time to start of relief of symptoms from an HAE attack. It is expressed in hours, begins in relation to the start of study treatment, and is assessed over a timeframe of up to 24 h. The registry states that subjects determined the start of relief by self-assessment. The endpoint applies to the intent-to-treat subject population, defined as all subjects admitted to the study who received any portion of study medication.
Time to relief is a time-to-event measure: the event is the reported start of symptom relief, and the recorded outcome is the elapsed time until that event. In general, such an endpoint can describe how quickly an event occurs without reducing the result to a simple yes-or-no outcome at a single time point. A median is a measure of the central timing in the observed population, while a confidence interval conveys uncertainty around the estimated median. These are general statistical descriptions, not findings from this trial.
The registry specifies a median and a 95% confidence interval for the primary measure, but neither value is reported in the registry record. The endpoint definition therefore indicates what was intended to be measured, not what the study observed. The record also does not report how subjects who did not report relief within the stated timeframe were handled in the analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the primary question and the study structure, but it does not provide the numerical primary outcome. The intended summary was the median time to start of relief, with a 95% confidence interval, among the intent-to-treat subject population. The actual median and confidence interval are not reported in the registry record. As a result, the posted information does not permit a description of the observed time to relief, the uncertainty around that estimate, or the range of timing compatible with the reported analysis.
This absence of a primary estimate also limits interpretation of the secondary outcomes. The registry names time to complete resolution of all HAE symptoms in the ITT subject population and in the ITT attack population. It does not give numerical results for these outcomes in the record described. The endpoint titles alone do not show the observed time to resolution, how many subjects or attacks contributed, or how precise any estimates were. Those findings are not reported in the registry record.
The single-group, non-randomized design is important to the kind of inference available. Without a concurrent randomized comparator, the study does not provide a like-for-like control contrast. Even if an outcome estimate were available, a change over time within this cohort would not by itself separate the effects of study treatment from other explanations. This is a general limitation of uncontrolled comparisons, not a claim that any particular alternative explanation occurred in this study.
The primary endpoint relies on subject self-assessment. In general, self-assessed symptom timing can capture a participant's experience directly, while also making the recorded event dependent on how that participant recognizes and reports relief. The open-label design is another relevant feature when considering subjective outcome measurement. The registry does not report a validation method or an independent assessment for the start of relief, so no further conclusion about measurement quality is warranted.
The record reports enrollment of 57, but does not report the number contributing data to the primary endpoint or the number of attacks represented in outcome analyses. Enrollment should not be treated as the analyzed sample size for a particular endpoint without that information. The record also does not report a numerical primary effect or an analysis result. Consequently, the posted information supports a description of the trial question, design, and specified endpoint, but not a conclusion about the size or precision of the observed primary outcome.
9. Statistical Methods Explained
The registry specifies a median and a 95% confidence interval for the primary endpoint. It does not report the numerical estimate or interval. The methods below explain these statistical concepts generally and distinguish the stated endpoint from results that are not reported in the registry record.
What does a median time describe?
In general, a median is a central summary: it marks the point at which half of the observations lie on either side, subject to the method used to estimate it. For a time-to-event outcome, the observations are times until a defined event. In this study the event is the subject-assessed start of relief from an HAE attack, and elapsed time is expressed in hours. A median time is different from an average time and does not describe every participant's experience. It also does not, by itself, convey the spread of individual times.
Time-to-event data can include participants for whom the event is not observed during the available observation period. General methods for these data can account for incomplete event times, but the registry record does not report the handling of such observations for this analysis. It would therefore be inappropriate to assume a particular censoring rule or estimation procedure beyond the stated median measure.
What does a confidence interval add?
In general, a confidence interval expresses uncertainty in an estimate under the assumptions of the statistical method used. The registry specifies a 95% confidence interval for the median time to relief. A narrower interval would indicate greater statistical precision than a wider interval, while neither width nor position can be assessed without the actual endpoints. A confidence interval is not a guarantee that the true value lies within the particular interval, and it is not a measure of the range of individual participant outcomes. These are general interpretations; the interval itself is not reported in the registry record.
Because the median and its interval are absent, no statement about the central observed time or its precision can be made from this record. An endpoint definition and a planned summary statistic are not a substitute for the reported estimate. The record also does not provide an analysis result from which a statistical test or other inferential conclusion could be described.
Why does the design affect interpretation?
In general, random allocation can help make treatment groups comparable at baseline, while a concurrent control provides a reference for interpreting outcomes over the same period. This study is described as non-randomized and single-group, with no masking. It therefore has no randomized concurrent control comparison. Observations from the group can describe what was recorded among its participants, but they do not alone estimate a contrast with an alternative treatment or with no study treatment.
The endpoint is based on self-assessment, and the study was open-label. In general, participants' knowledge of study treatment and their own judgments may be relevant to subjective outcome measurement. This is a methodological consideration, not evidence that reports were biased or inaccurate. The registry does not report details that would support a more specific assessment of this issue.
How should planning illustrations be read?
The planning assumptions describe an illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not a description of the actual single-group extension design. The record does not report a sample-size justification for the extension, and the planning illustration should not be treated as the trial's own design rationale or as observed power. Planning sample sizes are hypothetical quantities for a proposed comparison, not an estimate of how likely the completed study was to detect an effect.
The record does not report the details needed to assess the underlying observed effect or its analysis in this discussion. No planning count should be read as an observed participant count. In particular, an illustration that assumes equal allocation between two arms does not transform this single-group study into a two-arm comparison. These distinctions are general principles for interpreting sample-size planning.
What can be concluded from the analysis information?
The registry lists 4 outcome measures and 0 analyses. The presence of outcome definitions does not establish that numerical estimates are available. For the primary outcome, the specified summary is clear, but the observed estimate is not reported in the registry record. The record also does not report a statistical analysis plan, the method for calculating the confidence interval, or procedures for handling incomplete outcome data. Without those details and the numerical results, statistical precision and analytic robustness cannot be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and secondary endpoints, but a multiplicity strategy is not reported in the registry record. In general, when multiple outcomes or comparisons are assessed, the possibility of chance findings across analyses can be relevant. The record does not state whether any adjustment or hierarchy was planned, so it is not possible to characterize how multiple outcomes were handled statistically. The outcome list alone does not establish that each endpoint was formally tested or that a particular error rate was controlled.
The primary population is defined as all subjects admitted to the study who received any portion of study medication. The registry also names an ITT attack population for the secondary endpoint of time to complete resolution of all HAE symptoms. The record does not provide a further definition of that attack population, nor does it report the number of subjects or attacks analyzed for either population. Enrollment of 57 is not necessarily the number contributing to every outcome.
A missing-data method, rules for incomplete follow-up, and handling of subjects without an observed relief event are not reported in the registry record. These details matter generally because they can affect which observations contribute to a time-to-event estimate and how uncertainty is calculated. No assumption about the method used is justified by the endpoint description alone.
The registry lists 4 outcome measures and 0 analyses. It does not report the numerical primary or secondary outcome findings in the record described. Thus, multiplicity procedures, analysis populations beyond the stated definitions, and missing-data handling remain unreported rather than inferable from the endpoint names.
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 |
|---|---|---|---|
| C1 Esterase Inhibitor | 1 | 57 | 1.8% |
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 |
|---|---|
| C1 Esterase Inhibitor | 25 of 57 |
Most frequent serious adverse event terms
| Event term | Organ system | C1 Esterase Inhibitor |
|---|---|---|
| Hereditary angioedema | Congenital, familial and genetic disorders | 1 of 57 |
| Staphylococcal infection | Infections and infestations | 1 of 57 |
Most frequent non-serious adverse event terms
| Event term | Organ system | C1 Esterase Inhibitor |
|---|---|---|
| Headache | Nervous system disorders | 5 of 57 |
| Nasopharyngitis | Infections and infestations | 3 of 57 |
| Abdominal discomfort | Gastrointestinal disorders | 2 of 57 |
| Abdominal pain | Gastrointestinal disorders | 2 of 57 |
| Influenza like illness | General disorders | 2 of 57 |
| Upper respiratory tract infection | Infections and infestations | 2 of 57 |
| Vulvovaginal mycotic infection | Infections and infestations | 2 of 57 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 57 |
| Hereditary angioedema | Congenital, familial and genetic disorders | 1 of 57 |
| Conjunctivitis | Eye disorders | 1 of 57 |
Serious events with the highest arm-level rate: hereditary angioedema (1.8%), staphylococcal infection (1.8%).
The adverse-event figures describe the C1 Esterase Inhibitor group, for which 57 subjects are listed as at risk. The record reports 1 subject with a serious adverse event and 25 subjects with other adverse events. These counts describe the registry's affected-subject fields; they do not provide event rates over person-time or explain how long each subject was observed. The registry lists hereditary angioedema and staphylococcal infection among the top serious-event terms, each at 1.8%. The record does not establish from these entries whether the terms occurred in the same or different subjects.
The serious-event count and the listed serious-event terms should not be treated as a complete narrative of each event. The registry record does not report the timing, duration, outcome, or relationship of the events to treatment. Deaths are not reported in the registry record. The figures are descriptive safety information from a single-group, open-label study; without a concurrent control, they do not provide a comparative estimate of risk. They also do not establish that an event was caused by the study treatment. The event counts should be interpreted within the scope and reporting detail of the record, not as a treatment comparison or a complete account of safety.
12. What the Result Does, and Does Not, Mean
The record describes a Phase 3 extension study with a clear primary question: the time from the start of study treatment to the subject-assessed start of relief from an HAE attack. It also describes the intended summary as a median with a 95% confidence interval and defines the primary intent-to-treat subject population. These details tell readers what the investigators intended to measure and how the primary outcome was framed.
They do not reveal the observed primary result. Neither the median time to relief nor its confidence interval is reported in the registry record. Numerical findings for the listed secondary outcomes are also not reported in the record described. There is therefore no basis in these posted results for describing the size, direction, or precision of the primary endpoint estimate. The endpoint specification should not be mistaken for evidence of a particular outcome.
The trial's non-randomized, single-group, open-label design also limits what its results could establish as a comparison. There is no concurrent randomized control group in the record. In general, outcomes observed in one group cannot, by themselves, isolate the effect of treatment from other influences over time. This design feature does not negate the descriptive value of observations from the cohort, but it constrains comparative inference.
The safety entries provide reported counts and serious-event terms, but they do not establish treatment causation or allow a controlled comparison. Details about the events and their follow-up are not reported in the registry record. The study description and safety fields are therefore useful for identifying the trial's scope and the information it records, while leaving important outcome and analytic details unavailable. The conclusions should remain limited to those documented features rather than extending to claims about treatment benefit or lack of benefit.
13. Why This Trial Matters Statistically
This study illustrates why statistical interpretation depends on both an endpoint definition and the corresponding result. The primary outcome is stated in terms of time to a subject-assessed event, with a median and confidence interval planned as its summary. Those choices communicate the intended estimand and uncertainty framework. But when the numerical estimate and interval are not reported in the registry record, the endpoint description cannot answer how long relief took in the observed cohort or how precisely that time was estimated.
The extension design is also statistically instructive. The study is non-randomized, single-group, and open-label, so it does not create a like-for-like randomized comparison. This is important when readers encounter outcome descriptions that might otherwise sound comparative. A single-group observation can describe the cohort, but it does not supply the same evidence as a controlled contrast. The distinction is especially relevant for a symptom endpoint assessed by participants themselves.
Planning illustrations require similar care. The stated assumptions include two-arm equal allocation, even though the trial is a single-group extension. Such an illustration is hypothetical and should not be mistaken for the design used in the completed study. It is also not observed power. Separating design assumptions from observed trial results helps prevent sample-size planning from being interpreted as evidence that an effect was or was not detected.
Finally, the record demonstrates the difference between listing outcomes and reporting analyses. It identifies outcome measures and an ITT population, but does not supply the primary numerical result, a full analysis description, or missing-data procedures. Statistically, those omissions limit assessment of effect magnitude, uncertainty, and robustness. Recognizing the boundary between recorded design information and unreported findings is central to a careful reading of this trial.
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.
Several limitations specific to this study follow from its design and the detail available in the registry record. It is a non-randomized, single-group extension with no masking and no concurrent control group. As a result, the design does not provide a randomized comparison with another treatment or a control condition. The record also does not describe a control group from the pivotal study as part of this extension; the summary states that the extension was planned for subjects who had participated in that earlier study.
The primary endpoint depends on self-assessment of when symptom relief begins. The record does not report an independent assessment method or further details about how relief was defined for participants. In general, subjective timing can vary with how people perceive and report symptoms. This identifies a measurement consideration, not a finding that the assessments were inaccurate.
The record reports enrollment of 57 but does not report the endpoint-specific analyzed sample size, the number of attacks contributing to the secondary ITT attack population, or the handling of incomplete observations. A missing-data strategy and the method used to calculate the primary confidence interval are not reported in the registry record. These gaps prevent detailed evaluation of the analysis population and uncertainty.
Most importantly, the primary median and 95% confidence interval are not reported in the registry record, and the listed secondary outcomes have no numerical findings in the record described. The event listings also lack details about timing, duration, outcome, and relationship to treatment. These limitations mean that the trial's endpoint definitions and descriptive safety entries can be presented, but the posted information does not support a detailed assessment of clinical outcome magnitude or comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: C1 Esterase Inhibitor in Hereditary Angioedema (HAE)(Extension Study) — NCT00292981.
- Registry record last updated 2015-05-07; status last verified 2011-10.
- Results first posted 2011-06-23.
- 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
NCT00292981 is a completed Phase 3, open-label, non-randomized, single-group extension study of C1 Esterase Inhibitor for hereditary angioedema. Enrollment was 57. The study started in 2005-08 and reached primary completion in 2010-02. CSL Behring is listed as sponsor.
The primary endpoint was time to start of relief of symptoms from an HAE attack, measured in hours and based on subject self-assessment. The specified summary was a median with a 95% confidence interval in the ITT subject population, over up to 24 h after treatment began. The median and confidence interval are not reported in the registry record. Secondary outcomes concerned time to complete resolution of all HAE symptoms in the ITT subject population and ITT attack population.
The record reports 1 subject with a serious adverse event and 25 with other adverse events among 57 at risk. The top serious-event terms are hereditary angioedema and staphylococcal infection, each reported at 1.8%. Deaths are not reported in the registry record. The study has no randomized comparator, and the record does not report the numerical primary outcome result, detailed analysis procedures, or missing-data methods.