Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS) (NCT00838513), a non-randomized phase 2 study. The primary outcome is Percentage of Patients With TMA Event-free Status.

2. Clinical Question

This question focuses on a composite status rather than a single laboratory measurement. It combines platelet-count change, plasma therapy while on eculizumab, and new dialysis into a definition of whether a participant remained free of specified TMA-related events over the stated period. The record describes the primary analysis as a proportion in the ITT population, with an exact binomial 95% confidence interval.

The registry record does not report the numerical primary endpoint result. It therefore does not establish from the information recorded whether, or how often, participants met the definition. Nor does the single-group design estimate how the endpoint would have differed under a separate comparator treatment or no treatment. The clinical question is about the observed proportion in this study population, not a randomized treatment effect.

3. Trial Design

This was a Phase 2, open-label, multicenter controlled clinical trial of eculizumab in adult patients with plasma therapy-sensitive aHUS. Although the official title includes the word “controlled,” the record identifies the allocation as non-randomized and the model as single group. No separate comparator arm is described. The design therefore does not provide a randomized, like-for-like comparison between eculizumab and another treatment or control condition.

The registry record lists enrollment as 15 and the study status as completed. The recorded start is 2009-07, and primary completion is 2010-10. Alexion Pharmaceuticals, Inc. is listed as the sponsor. These details describe the trial record; they do not indicate when individual participants entered or completed follow-up.

Because masking was listed as none and the study was open label, treatment assignment was not concealed from participants and study personnel through blinding. The record does not report additional details about how participants entered the study, how treatment was administered, or what procedures were used to reduce bias in outcome assessment. Those details are not reported in the registry record.

The primary endpoint was the percentage of participants with TMA event-free status through 26 weeks. The registry specifies the ITT population for the proportion analysis and an exact binomial 95% confidence interval. Secondary outcomes include TMA intervention rate, platelet-count change from baseline at 26 weeks and 156 weeks, platelet-count normalization, TMA event-free status, hematologic normalization, and complete TMA response. The listed outcome names do not supply their numerical results. Although 13 outcome measures and 12 analyses are recorded, the statistical analysis plan, including any prespecified handling of multiple endpoints, is not reported in the registry record.

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: Patients receiving PT for aHUS and observed to receive ≥ 1 PT every two weeks, and no more than 3 PT treatments/week for at least 8 weeks before the first dose of eculizumab. Patients who met the eligibility criteria during the Observation Period were enrolled into the Treatment Period which commenced with the first eculizumab dose.

Screening Period

Reasons for not completing this period:

Observation Period (8 Weeks)

Treatment Period (26 Weeks)

Extension Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The tabulations of the proportions of patients who achieved a TMA Event-Free status through 26 weeks were performed for the ITT population. Exact binomial 95% confidence intervals were produced for the analysis.

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: The intent-to-treat (ITT) population was defined as all patients who received any amount of eculizumab, and were considered evaluable for safety and efficacy analyses. For both the efficacy and safety analyses, all 20 patients who were treated with study drug were included in the ITT population.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients With TMA Event-free Status, measured over Through 26 weeks.

The primary endpoint is the percentage of participants with TMA event-free status through 26 weeks. The registry defines this status as the absence for at least 12 weeks of three specified events: a platelet-count decrease greater than 25% from the Platelet Count Pre-PT Baseline Set Point; PT while the participant is receiving eculizumab; and new dialysis. This combines clinical and laboratory criteria into one binary outcome: each participant either meets the event-free definition or does not, according to the recorded criteria.

A composite endpoint can summarize whether several specified events occurred, rather than treating each event as the sole measure of outcome. Its meaning depends on the components and time requirements in its definition. In this case, the endpoint describes a defined event-free status; it should not be read as a direct measure of every aspect of disease activity, functioning, or safety.

The registry says the endpoint proportion was tabulated in the ITT population and that an exact binomial 95% confidence interval was produced. The interval communicates uncertainty around the estimated proportion. The numerical proportion and its interval are not reported in the registry record, so the endpoint’s observed frequency and precision cannot be described from the recorded information. The endpoint definition is available, but its numerical result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a percentage of participants with TMA event-free status through 26 weeks. This is a binary-outcome analysis: each participant is classified according to whether the specified endpoint definition is met. The resulting proportion is an estimate of the frequency of that status in the analysis population. It is not a comparison of treatment groups, because the record lists a single-group model and no separate comparator.

What does the confidence interval express?

The record says an exact binomial 95% confidence interval was produced for the primary proportion. In general, a confidence interval gives a range of values compatible with the data and the method used, reflecting sampling uncertainty. It is not a guarantee that the true value lies in the particular interval, nor does it address every source of uncertainty. For example, an interval cannot correct for selection bias, outcome misclassification, or limits in the study design.

An exact binomial interval is based on the binomial model for a count of participants meeting an outcome definition among those assessed. It is often used for proportions, particularly when the available count is limited, because it does not rely on the same large-sample approximation used by some other interval methods. The registry record does not report the numerical proportion, interval limits, or the number of participants contributing to the primary endpoint calculation. Consequently, the interval’s width and the estimate’s precision cannot be evaluated from the recorded information.

What does the endpoint definition contribute?

The event-free endpoint is not simply the absence of any one event. It requires the specified conditions to be absent for at least 12 weeks, and includes a platelet-count decrease greater than 25% from the stated baseline set point, PT while receiving eculizumab, and new dialysis. Each element contributes to the classification. The definition helps readers understand what the percentage represents, but the record does not provide component-level results or further operational details about how the criteria were assessed.

In general, endpoint definitions matter because different definitions can classify participants differently. A composite measure can capture more than one type of event in a single summary, but the combined result does not reveal which component contributed most. For this study, separate counts or analyses for the endpoint components are not reported in the registry record.

How should a single-group result be understood?

For a single-group study, a proportion describes the observed outcome frequency among participants in that group. It is not a treatment-versus-control contrast. A comparison intended to estimate a causal treatment effect must address how outcomes would have differed under another treatment condition, which the single-group record cannot directly show. In general, observed outcomes can also reflect participant characteristics, the natural course of illness, co-interventions, measurement practices, and follow-up. The registry record does not report enough detail to assess these influences.

Non-randomized allocation means assignment was not described as random. Randomization, in general, helps balance known and unknown prognostic factors across comparison groups. Since no comparison group is recorded here, neither randomization nor adjustment between arms is applicable to the primary proportion as described. Whether other methods were used to address confounding is not reported in the registry record.

What can the secondary outcomes add?

The record lists outcomes covering TMA intervention rate, platelet-count change, platelet-count normalization, TMA event-free status, hematologic normalization, and complete TMA response. It also lists platelet-count change at 156 weeks. These outcomes can address different aspects of disease-related status or follow-up in general, but their titles alone do not provide findings. Numerical estimates, denominators, uncertainty intervals, and analysis details for these outcomes are not reported in the registry record.

Multiplicity arises when many outcomes or analyses are examined. In general, the more statistical questions considered, the greater the chance that at least one result may appear notable by chance if interpretation does not account for the analysis strategy. The registry records 13 outcome measures and 12 analyses, but the statistical plan for prioritization, adjustment, or interpretation is not reported. No particular correction or hierarchy should therefore be assumed.

What do the planning illustrations mean?

Any sample-size planning figures associated with the posted results are illustrations based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations describe hypothetical planning under those assumptions. They are not observed power, and they do not turn this single-group trial into a two-arm comparison. The registry record does not report the trial’s own sample-size justification or statistical plan, and the observed effect needed to interpret a planning illustration is not reported in the registry record.

In general, power is a design property tied to assumptions about the effect, variability, significance threshold, and analysis. A post hoc calculation based on an observed effect does not establish the probability that the study would detect a true effect, nor does it remedy a missing comparator. The planning assumptions should therefore be kept separate from the trial’s actual design and observed results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Eculizumab")
n      <- c(20)
events <- c(16)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Eculizumab  20  16  80.0  56.3  94.3  58.4  91.9  58.1  91.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 12 analyses, including a primary TMA event-free endpoint and several secondary measures. The record does not report how the endpoints were prioritized beyond identifying the primary outcome, whether secondary outcomes were exploratory or confirmatory, or whether any multiplicity adjustment was planned. Without those details, a reader cannot determine the intended interpretation of results across the full set of outcomes. No particular adjustment, testing hierarchy, or family of hypotheses should be inferred.

The primary endpoint analysis is described for the ITT population, with an exact binomial 95% confidence interval. The registry record does not report how missing primary endpoint observations were handled, how many participants had missing data, or whether any sensitivity analyses were performed. It also does not report the amount or pattern of missingness for secondary outcomes. This matters because estimates based on observed participants may be affected if outcome availability is related to participants’ outcomes or characteristics. The direction and size of any such effect cannot be determined without information about missingness and its handling.

The ITT label identifies the stated analysis population, but the record does not provide additional details about its operational definition or how participants were included in each analysis. The registered enrollment is 15, while the adverse-event record lists 20 at risk; the reason for that discrepancy is not reported in the registry record. It should remain an unresolved reporting difference rather than being interpreted as evidence about the endpoint population or a particular analysis rule.

In general, transparent reporting of populations, missing-data procedures, and multiplicity plans helps readers judge how estimates were produced and how much confidence to place in multiple findings. Those details are not reported in the registry record. The numerical primary endpoint result is also not reported, so its estimate and uncertainty cannot be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (10.0%), renal failure chronic (10.0%), pericardial effusion (5.0%), gastrointestinal haemorrhage (5.0%), impaired gastric emptying (5.0%).

The registry’s serious adverse-event entries list an Eculizumab group with 20 participants at risk and 13 affected. Listed serious-event terms are pneumonia, 10.0%; renal failure chronic, 10.0%; pericardial effusion, 5.0%; gastrointestinal haemorrhage, 5.0%; impaired gastric emptying, 5.0%; and medical device complication, 5.0%. These are descriptive entries in the registry record, not evidence by themselves that eculizumab caused any listed event.

The record also contains other adverse-event fields listing 20 at risk and 20 affected. Their relationship to the serious-event fields is not explained in the registry information, so the entries should be read as separately recorded fields rather than combined or reconciled. The registry enrollment is 15, which does not match the at-risk count of 20 in the adverse-event fields; the reason is not reported in the registry record. These values should not be converted into a new denominator or an adjusted rate.

There is no separate comparator group recorded, so the serious-event entries cannot show whether event occurrence was higher or lower than under another treatment condition. Deaths are not reported in the registry record. The entries also do not supply information about event timing, duration, severity beyond the registry category, or individual-level overlap among event terms.

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

The registry record establishes that this was a completed Phase 2, open-label, single-group study of eculizumab in adults with plasma therapy-sensitive aHUS. It specifies a primary endpoint, a time frame, a population for the primary proportion analysis, and an exact binomial confidence-interval method. Those details clarify the question the trial set out to address and how the primary endpoint was intended to be summarized.

However, the numerical primary endpoint result and its confidence interval are not reported in the registry record. The endpoint’s observed frequency and precision therefore cannot be described. The listed secondary outcome names also do not provide numerical findings. This means the record, as described, cannot support a numerical statement about how often the primary status occurred or about changes in the secondary measures.

The design does not provide a randomized comparator. In general, a single-group outcome can describe what was observed among participants, but cannot isolate the effect of treatment from other possible explanations for outcomes. This record therefore cannot establish a comparative treatment effect against another therapy or no treatment. The open-label design also means masking was not used; the registry record does not describe additional protections against bias in outcome measurement.

The serious adverse-event entries are useful as descriptive safety information recorded for the study, but they do not prove causation. The absence of a comparator, the unreported reason for the difference between enrollment and adverse-event at-risk counts, and the lack of reported event-level details limit interpretation. The record also does not report deaths.

These limitations do not negate the value of clearly defining a clinical endpoint or recording safety events. They do mean that conclusions must stay within the available information: the trial design and endpoint are described, while the primary numerical result, comparative effect, and several details needed to assess precision and safety are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a registry can define a proportion-based primary endpoint while leaving important interpretive elements dependent on the design and completeness of the results. The endpoint is explicitly framed as TMA event-free status through 26 weeks, with a stated definition and an exact binomial confidence interval in the ITT population. That is more specific than a broad label alone: it tells readers which clinical and laboratory criteria contribute to the classification and the period to which it applies.

At the same time, the trial is listed as single group and non-randomized. This distinction matters because a proportion in one group is not a comparative treatment effect. The endpoint can be described using an interval, but neither an interval nor a precise proportion would supply the missing counterfactual comparison. Statistical precision and causal interpretation are separate issues.

The record also illustrates why endpoint multiplicity and analysis transparency matter. It lists 13 outcome measures and 12 analyses, but does not report how secondary analyses were prioritized or whether multiplicity was addressed. Without that context, readers cannot know how the different outcomes were intended to support conclusions. Similarly, the ITT population and exact interval method are named, but missing-data procedures and the numerical endpoint result are not reported.

Finally, safety entries require careful attention to their recorded denominators and categories. The adverse-event fields list 20 at risk, while enrollment is listed as 15, and the reason is not reported. Treating those entries as self-explanatory would obscure a material reporting uncertainty. Statistically, the case highlights the value of reading design, outcome definition, denominator, precision, and analysis transparency together rather than treating any one result as a complete account.

15. 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 numerical result is not reported in the registry record. Although the endpoint definition, ITT population, and exact binomial confidence-interval method are described, the proportion and interval limits are absent. The estimate’s magnitude and precision therefore cannot be assessed. Numerical findings for the listed secondary outcomes are also not reported.

The single-group, non-randomized design lacks a separate comparator. It can describe outcomes in the study group but cannot directly estimate a difference against another treatment or control condition. The study was open label and had no masking. The registry record does not report details that would allow assessment of how outcome evaluation may have been protected from bias.

The enrollment value is 15, but adverse-event fields list 20 participants at risk. The reason for this difference is not reported in the registry record. The available information also does not explain whether the at-risk counts relate to a different analysis population or reporting convention. No reconciliation should be assumed.

Other limitations include missing information about missing-data handling, endpoint component results, and the statistical plan for multiple outcomes. The record does not report a sample-size justification, interim analyses, or further methods for addressing confounding. It also does not report event timing or participant-level overlap for the serious adverse-event terms. These absences restrict interpretation but do not imply that any particular procedure was or was not used outside what the registry records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS) — NCT00838513.
• Registry record last updated 2015-07-23; status last verified 2015-06.
• Results first posted 2015-01-26.
• 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.

19. Record Summary

The registry record describes a completed Phase 2, open-label, multicenter, non-randomized, single-group study of eculizumab in adults with plasma therapy-sensitive aHUS. Enrollment is listed as 15. The recorded start is 2009-07 and primary completion is 2010-10; Alexion Pharmaceuticals, Inc. is listed as sponsor.

The primary endpoint is the percentage of participants with TMA event-free status through 26 weeks, analyzed in the ITT population with an exact binomial 95% confidence interval. The numerical primary result is not reported in the registry record. The listed secondary outcomes cover TMA interventions, platelet-count measures, event-free status, hematologic normalization, and complete TMA response.

Serious adverse-event entries are recorded, but the at-risk count differs from the enrollment value, and the reason is not reported. With no separate comparator group, the record describes a single-group study rather than a randomized comparison.