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, Safety and Tolerability of Icatibant for the Treatment of HAE (NCT01457430), a na phase 4 study. The primary outcome is Time to Complete or Near Complete Resolution From Onset of Symptoms.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01457430 |
| Phase | Phase 4 |
| Condition | Hereditary Angioedema |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with hereditary angioedema experiencing an acute attack. The registry lists 19 participants enrolled. It does not report further eligibility details or a description of the population included in the primary outcome analysis.
Intervention
Self-administered subcutaneous icatibant for an acute attack. The record describes an open-label study intended to evaluate efficacy, safety, local tolerability, and convenience.
Comparator
There is no concurrent comparator group in the registry design: the study is listed as single-group, with allocation and masking recorded as not applicable and none. The summary mentions treatment in a medical facility as a reference for the investigators’ expectation, but the record does not describe a medical-facility control arm.
Primary question
How long does it take from the onset of an attack to complete or near-complete symptom resolution, as reported by the patient, when icatibant is self-administered? The record also describes an expectation that self-administration would not change this time compared with treatment in a medical facility. It does not report a comparative analysis that tests that expectation.
The distinction between the stated research question and the listed design is important. A single-group study can describe outcomes observed among participants receiving the intervention, but it cannot directly estimate a difference against a concurrent medical-facility group. The registry record identifies the study as phase 4 and completed, but completion status alone does not supply an outcome estimate. The listed primary endpoint is a patient-reported time measured in minutes; the numerical result and its uncertainty are not reported in the registry record.
3. Trial Design
The registry describes a phase 4, open-label, multicenter study of a self-administered subcutaneous formulation of icatibant for acute hereditary angioedema attacks. It lists Massachusetts General Hospital as the sponsor, enrollment of 19, and study status as completed. The listed start is 2011-12 and primary completion is 2014-04. The intervention entry is icatibant, and the arm description is “Open-label study.”
The design is recorded as single-group, with allocation marked not applicable and masking marked none. These entries mean the registry does not describe random assignment or a blinded comparison. The single-group structure is central to interpreting the results: the record can describe the treated group, but it does not provide a contemporaneous control group for estimating how outcomes might differ under another care setting.
The brief summary says the investigators proposed evaluating safety, local tolerability, convenience, and efficacy. It also states their expectation that self-administration would not change the time to complete or near-complete symptom resolution compared with administration in a medical facility. That expectation is not itself evidence of equivalence, and the registry does not report a formal equivalence or noninferiority framework, a margin, or a statistical comparison with a medical-facility group.
The record lists two outcome measures and no analysis entries. It does not describe the recruitment process, eligibility criteria, dosing details, follow-up procedures, protocol deviations, or the statistical plan. Those details are not reported in the registry record, so the design description should remain limited to the listed features rather than filling in likely procedures.
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 | Icatibant |
|---|---|
| STARTED | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 0 |
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 | Icatibant |
|---|---|---|
| Participants analysed | 19 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 |
| Age, Categorical: >=65 years | Participants | 2 |
| Age, Continuous | years | 41 (19 to 69) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: United States | participants | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Complete or Near Complete Resolution From Onset of Symptoms, measured over Time to complete or near complete resolution of symptoms as reported by the patient, an expected average of 8-10 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | minutes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is time from the onset of hereditary angioedema symptoms to complete or near-complete resolution, reported by the patient. The registry says the time of symptom onset, time of icatibant administration, and time of complete relief were recorded in minutes. Its endpoint definition starts the clock at symptom onset, rather than at the time of drug administration. This matters when interpreting the measure: it represents the attack-to-relief interval, not solely the interval after treatment.
Time to symptom resolution is useful as a patient-centered measure because it describes how long symptoms persist before the stated endpoint is reached. A median can summarize a distribution of times without being dominated as strongly by unusually long observations as a mean may be. The registry identifies the planned summary as a median with an interquartile range. In general, the interquartile range describes the middle portion of the observed distribution and helps show how variable participants’ times were around the median.
The timeframe is described as time to resolution as reported by the patient, with an expected average of 8-10 hours. That wording is a timeframe description, not a reported result. The registry record does not report the median, interquartile range, number of participants contributing endpoint data, or a statistical analysis of the endpoint. Consequently, the endpoint’s observed value and precision cannot be assessed from the posted record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry provides design and endpoint information, but it does not provide a numerical primary outcome result. Although the primary endpoint is specified as a median time with an interquartile range, neither summary is reported in the registry record. The posted results therefore do not show how long participants took to reach complete or near-complete symptom resolution, or how much those times varied.
The distinction between the endpoint definition and the proposed comparison also matters. The endpoint begins at symptom onset, while the record separately says the time of icatibant administration was recorded. That may allow researchers to describe more than one interval, but the registry does not report an analysis of time from administration to relief. It also does not report a comparison with treatment in a medical facility. The investigators’ expectation about no change in resolution time is a statement of expectation, not a result established by the listed design.
The trial is listed as single-group and open-label. In general, a single-group study can report outcomes among people receiving an intervention, but it cannot separate the intervention’s association with those outcomes from other influences using a concurrent control. Open-label reporting also means the record does not describe masking of participants or investigators. These design features do not make descriptive observations meaningless, but they limit the kinds of comparative conclusions that can be drawn.
The safety summary lists 78 at risk and 0 affected for serious adverse events, and 78 at risk and 4 affected for other adverse events. These are registry summary counts; they are not a substitute for event descriptions, severity, timing, or a comparator. The record does not identify serious adverse event terms. Deaths are not reported in the registry record.
In short, the registry supports a description of the study’s purpose, structure, endpoint definition, and listed safety counts. It does not provide the primary outcome estimate, uncertainty interval, analysis population, or a controlled comparison. The tables, plots, and planning illustrations should be read alongside that limitation: they cannot turn an unreported outcome analysis into evidence about the magnitude or precision of the treatment-group result.
9. Statistical Methods Explained
The registry labels the primary measure as a median with an interquartile range. This tells readers the kind of summary intended, but it does not show that the analysis was completed or how it was implemented. No primary outcome analysis is listed in the registry record. The observed median and interquartile range are not reported, and the record does not describe an estimator, confidence interval, or model.
What does a median summarize?
In general, the median is the middle value when observations are ordered. It is often useful for time measurements because a small number of very long times can pull the arithmetic mean upward. The interquartile range conveys the spread of the central part of the observations. Together, the median and interquartile range can describe both a typical observed time and its variability, but they do not by themselves provide a confidence interval for the median or quantify uncertainty about the estimate. A confidence interval, in general, gives a range of values compatible with the data under a specified statistical procedure. No such interval is reported.
What does the endpoint clock measure?
The endpoint is defined from symptom onset to complete or near-complete resolution, based on the patient’s report. The record says onset, administration, and relief times were recorded in minutes. Because the endpoint starts at onset, it includes the interval before administration as well as the interval after administration. The registry does not provide separate estimates for those intervals. General interpretation should therefore keep the defined clock in view and avoid treating the endpoint as a measure of time after dosing alone.
What can a single-group design estimate?
In general, a single-group study can describe outcomes observed in the enrolled group. A comparison between treatment strategies requires a suitable contrast. Without a concurrent medical-facility group in this record, the outcome under self-administration cannot be directly contrasted with an outcome observed under medical-facility treatment within the same study. A historical or external comparison would require additional information and assumptions; the registry does not report such an analysis. The stated expectation that self-administration would not change resolution time does not establish that the study was designed or analyzed as an equivalence or noninferiority trial.
How should the planning illustrations be read?
The page includes calculated sample-size illustrations based on an observed effect. The record states that these are planning illustrations, not the trial’s own design, and describes a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, such illustrations ask how much information a hypothetical design might need to detect a chosen effect under specified assumptions. They are not observed power, do not describe the actual single-group enrollment plan, and do not establish what effect the trial found. The record does not report a design-stage sample-size justification or the assumptions used by the investigators.
Because the trial has no listed comparison arm, planning calculations framed around two equally allocated arms should not be mistaken for a description of this study’s actual design. If an illustration uses a fraction of an observed effect, it is a sensitivity exercise about hypothetical effects. It does not add a comparator, recover missing outcome results, or establish the precision of the trial’s observed endpoint.
What is not available for evaluating the analysis?
The registry does not report the analysis population, handling of missing endpoint times, treatment of withdrawals, or a statistical model. It does not state whether any interim analyses were planned or performed, or whether any adjusted analysis was used. These items are not reported in the registry record. Their absence means readers cannot determine from this record whether all enrolled participants contributed to the endpoint, how incomplete reports were handled, or whether the analysis followed a prespecified plan.
More generally, statistical methods should be interpreted in relation to the question they answer. A descriptive median addresses the distribution of times in the observed group; a comparative estimate addresses a difference between groups; and a confidence interval addresses uncertainty around an estimate. Those are distinct tasks. Here, the record identifies the intended descriptive summary but does not report its value or an inferential analysis, so the posted information does not support a quantitative assessment of the primary outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary endpoint as time from symptom onset to complete or near-complete resolution. It also lists percent change in VAS scores as a secondary outcome and identifies two outcome measures overall. No numerical result for either measure is reported in the registry record.
When a study assesses more than one outcome, multiplicity can arise if several hypotheses are tested and the results are interpreted as confirmatory. In general, testing multiple outcomes without an appropriate plan can increase the chance of a false-positive finding across the set of tests. Whether that issue applies, and how it was handled, depends on the prespecified analysis plan. The registry does not report a multiplicity adjustment, a hierarchy of tests, or whether any listed outcome was considered confirmatory beyond its designation as primary or secondary.
Missing-data methods and analysis populations are also not reported in the registry record. The record does not say how a missing onset time, missing relief time, or incomplete VAS assessment would be handled. It does not identify an intention-to-treat, per-protocol, or other analysis population. Without these details, readers cannot establish how many participants contributed to each outcome or whether the analysis included everyone enrolled.
The registry contains no listed analysis entries. This does not prove that no analyses were performed; it means the posted record does not document them. Interim analyses, stopping rules, protocol deviations, and sensitivity analyses are not reported in the registry record. As a result, it is not possible to judge from this record whether outcome selection, missing data, or analysis decisions could have affected the reported findings. No findings for the listed outcomes are posted to evaluate.
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 |
|---|---|---|---|
| Icatibant | 0 | 78 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Icatibant | 4 of 78 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Icatibant |
|---|---|---|
| Fatigue | Blood and lymphatic system disorders | 1 of 78 |
| Fever | Blood and lymphatic system disorders | 1 of 78 |
| Dizziness | Nervous system disorders | 1 of 78 |
| Nausea | Gastrointestinal disorders | 1 of 78 |
The registry safety summary lists the icatibant group with 78 at risk for serious adverse events and 0 affected. For other adverse events, it lists 78 at risk and 4 affected. These are the figures as recorded; the registry does not provide descriptions of the other adverse events in this summary. It also lists no serious adverse event terms.
These counts should be read as a registry summary, not as a complete account of safety. The record does not report event onset, duration, severity, relationship to treatment, resolution, or whether a participant experienced more than one event. It does not provide a comparator group, so the figures cannot establish how event occurrence compares with another treatment or care setting. The record lists 78 at risk, while enrollment is 19; it does not explain the relationship between these counts, so they should not be treated as an unexplained participant denominator.
Deaths are not reported in the registry record. That is different from a statement that no deaths occurred. More generally, a count of zero affected in the serious-event summary does not show that serious harms are impossible, nor does it provide a precise estimate of risk. Interpretation depends on the population observed, duration and completeness of follow-up, and event ascertainment; those details are not reported.
12. What the Result Does, and Does Not, Mean
The posted record establishes that this was a completed, open-label, single-group phase 4 study of self-administered icatibant for acute hereditary angioedema attacks. It identifies a patient-reported primary endpoint: time from symptom onset to complete or near-complete resolution. It also describes the investigators’ interest in safety, local tolerability, convenience, and efficacy.
The record does not, however, report the primary endpoint result. It gives no median or interquartile range, no confidence interval, and no comparative estimate against medical-facility administration. The investigators’ stated expectation that self-administration would not change resolution time is not a demonstrated finding. Without a reported result and a concurrent comparator, readers cannot assess either the observed time to resolution or whether it differed from an alternative approach.
The safety summary reports the listed serious and other adverse-event counts, but it does not provide event descriptions or sufficient context to compare safety across approaches. The absence of serious adverse events in the summary should not be generalized beyond the recorded data or interpreted as evidence that serious events cannot occur. Likewise, the other-adverse-event count alone does not describe severity or clinical course.
In general, a study’s result is more informative when the estimate, uncertainty, analysis population, and methods are available. Here, those outcome-analysis details are not reported in the registry record. The appropriate conclusion is therefore about the limits of the posted information: it describes the study question and design, but does not permit a quantitative judgment about the primary outcome or a comparative claim. The sample-size illustrations elsewhere on the page are planning exercises and do not fill that evidentiary gap.
13. Why This Trial Matters Statistically
This study illustrates why the design and the question need to be read together. The investigators’ stated interest included whether self-administration changed the time to symptom resolution compared with treatment in a medical facility. Yet the registry lists a single-group study, without a concurrent medical-facility arm. That structure can support description of the enrolled group, but it cannot by itself provide a direct between-setting estimate.
The endpoint definition also has an important statistical feature: the clock starts at symptom onset, even though administration time was recorded separately. That makes the endpoint a measure of the full onset-to-relief interval, rather than an interval defined solely by treatment administration. Clearly identifying the starting point helps prevent readers from attributing the entire measured duration to the treatment period.
The record is also a useful example of the difference between outcome specification and outcome reporting. It names a median and interquartile range for the primary endpoint, but provides neither value. A planned summary does not show what the observed data were, and a completed study status does not supply an analysis. The same distinction applies to the listed secondary VAS outcome and safety summary.
Finally, the record demonstrates why planning illustrations must be kept separate from observed evidence. Sample-size illustrations can explore hypothetical designs under stated assumptions, but they are not the trial’s actual design or a substitute for outcome estimates. With no listed outcome analyses, the most statistically responsible reading is to describe what the registry records and state clearly which questions remain unanswered.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this particular study is the mismatch between the proposed comparison in the brief summary and the listed single-group design. The summary refers to treatment in a medical facility as a point of comparison, but the registry does not describe a concurrent control arm or a comparative analysis. The expectation of no change in resolution time therefore cannot be assessed as a treatment contrast from the posted design.
The registry does not report the primary outcome estimate, its interquartile range, or a confidence interval. It also does not report how many participants contributed primary endpoint data, whether reported resolution times were complete, or how missing or ambiguous patient reports were handled. The listed enrollment of 19 does not establish the analysis sample for this endpoint.
Although onset, administration, and relief times are described as recorded, no separate administration-to-relief result is reported. The primary endpoint begins at symptom onset, and interpretation cannot isolate the period after treatment from the full attack-to-relief interval using the posted information.
The study is open-label and single-group, and the record does not describe masking or a control comparison. The registry also does not report detailed eligibility criteria, dosing procedures, follow-up completeness, protocol deviations, or an analysis plan. These details are not reported in the registry record and should not be inferred.
For safety, the summary has limited contextual detail: the serious-event terms are not listed, other adverse events are not described, and deaths are not reported. The relationship between the at-risk counts and enrollment is not explained. These omissions prevent a fuller assessment of event types, follow-up, and denominators from the registry summary alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy, Safety and Tolerability of Icatibant for the Treatment of HAE — NCT01457430.
- Registry record last updated 2016-10-18; status last verified 2016-10.
- Results first posted 2016-10-18.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01457430 is listed as a completed phase 4, open-label, multicenter, single-group study sponsored by Massachusetts General Hospital. The registry lists enrollment of 19 and an intervention of self-administered subcutaneous icatibant for acute hereditary angioedema attacks. The study start is recorded as 2011-12 and primary completion as 2014-04.
The primary endpoint is patient-reported time from symptom onset to complete or near-complete symptom resolution, intended to be summarized by a median and interquartile range. Percent change in VAS scores is listed as a secondary outcome. Numerical outcome results and analysis details are not reported in the registry record.
The safety summary lists 0 affected for serious adverse events and 4 affected for other adverse events, with 78 at risk in each category. Serious adverse event terms are not listed, and deaths are not reported in the registry record. The single-group design does not provide a concurrent comparison with treatment in a medical facility.