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 Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment (NCT02614898), a registered phase not stated study. The primary outcome is Rate Of Thrombotic Microangiopathy (TMA) Manifestations During Eculizumab Treatment Compared To Off-Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02614898 |
| Phase | Phase not stated |
| Condition | Atypical Hemolytic Uremic Syndrome |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 67 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alexion Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled pediatric and adult participants with atypical hemolytic uremic syndrome (aHUS). The primary outcome population was all enrolled participants. The registry record reports enrollment of 67 participants and states that enrollment reached only 20% of the planned total.
Intervention
Eculizumab treatment was given at the discretion of the treating physician. The study was open-label and observational with respect to treatment; participants were not randomized to receive or avoid eculizumab. Treatment therefore reflected clinical care rather than a study-assigned regimen.
Comparator
The primary question compares TMA manifestation rates during eculizumab treatment with rates during off-treatment periods. The registry record also describes participants with aHUS with or without eculizumab treatment. These periods or groups are not a randomized, like-for-like control comparison.
Primary question
The study aimed to assess disease manifestations of complement-mediated thrombotic microangiopathy and potential clinical predictors of manifestations and progression. The primary outcome was the rate of TMA manifestations during treatment compared with off-treatment, over the stated baseline-to-24-month timeframe. No summary-level outcome data were generated.
3. Trial Design
This was a prospective, open-label study in participants with aHUS. The registry record describes no participant randomization. Eculizumab treatment was observational and left to the treating physician, so the study did not assign participants to treatment and control arms under a randomized protocol. The recorded intervention is eculizumab, categorized as other.
The registry lists 67 enrolled participants and classifies the study as terminated. Its start date was 2015-11-04, and its primary completion date was 2017-10-05. The record states that the study stopped with only 20% of planned enrollment because funding for the program was subsequently lost. It does not state the planned enrollment total or give a detailed account of when or how the termination decision was made.
The study sought to assess disease manifestations of complement-mediated TMA and potential clinical predictors of disease manifestations and progression in participants with aHUS, with or without eculizumab treatment in clinical care. The outcome timeframe is baseline and 24 months. Secondary outcomes listed in the record are change from baseline to 24 months in estimated glomerular filtration rate and incidence of plasma exchange and plasma infusion.
All participants enrolled in ECU-aHUS-403 were concurrently enrolled in protocol M11-001. The registry record says their data would be included in analyses for M11-001. It also states that samples collected for outcome assessment in this study could not be analyzed to generate summary-level data. No statistical analysis results are posted for this study.
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: Sixty-seven participants were enrolled in this study (15 pediatric and 52 adults). Treatment information was missing for 1 adult participant.
Overall Study
| Stage | Pediatric | Adult |
|---|---|---|
| STARTED | 15 | 52 |
| Safety Population | 15 | 52 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 15 | 51 |
Reasons for not completing this period:
| Reason | Pediatric | Adult |
|---|---|---|
| Participated until study termination | 10 | 26 |
| Lost to Follow-up | 0 | 2 |
| Physician Decision | 1 | 8 |
| Study Terminated by Sponsor | 3 | 0 |
| Withdrawal by Subject | 0 | 2 |
| Withdrawal by Parent/Guardian | 1 | 1 |
| Other-Additional Information Unavailable | 0 | 11 |
| Missing | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants. The study was terminated with only 20% of the planned enrollment; because the program lost funding, samples collected could not be analyzed to generate summary-level data. All participants enrolled in ECU-aHUS-403 were concurrently enrolled in protocol M11-001, and their data will be included in the analyses for M11-001.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: All enrolled participants.
| Characteristic | Unit | Pediatric | Adult | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 52 | 67 | |
| Age, Continuous | years | 7.9 (SD 3.46) | 43.3 (SD 17.26) | 35.4 (SD 21.33) |
| Sex: Female, Male: Female | Participants | 6 | 34 | 40 |
| Sex: Female, Male: Male | Participants | 9 | 18 | 27 |
| Race/Ethnicity, Customized: Caucasian | Participants | 12 | 44 | 56 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 2 | 3 |
| Race/Ethnicity, Customized: Black | Participants | 1 | 5 | 6 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Rate Of Thrombotic Microangiopathy (TMA) Manifestations During Eculizumab Treatment Compared To Off-Treatment, measured over Baseline, 24 Months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the rate of TMA manifestations during eculizumab treatment compared with off-treatment. The registry gives a timeframe of baseline and 24 months. It defines a manifestation as a hematologic or renal event due to aHUS, extra-renal clinical signs or symptoms of aHUS, or tissue biopsy demonstrating TMA due to aHUS.
In general, an endpoint that groups manifestations across organ systems can capture more than one kind of disease event. This definition includes clinical events and tissue evidence, rather than restricting the outcome to a single laboratory measure. A rate comparison also aims to relate manifestations to periods of treatment exposure, although the registry record does not report the rate calculation, exposure-time details, or a statistical model.
The endpoint was intended to address whether the observed frequency of TMA manifestations differed between treatment and off-treatment periods in the clinical setting. Because treatment was chosen by treating physicians and was not randomized, such a comparison would not by itself isolate a causal treatment effect. In this study, no summary-level primary endpoint data were generated: the record states that collected samples could not be analyzed after termination and loss of program funding. An estimated rate, treatment contrast, confidence interval, and significance test are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record contains no summary-level results for the primary outcome. It gives the endpoint definition and timeframe but no event counts, rates, contrast between treatment and off-treatment, or measure of uncertainty. Consequently, the record does not establish the direction or size of any difference in TMA manifestations. It also does not provide an estimate precise enough to judge how compatible the data might be with different possible effects.
The study enrolled 67 participants, but the record says this represented only 20% of planned enrollment. The study was terminated, and funding loss prevented analysis of the collected samples for outcome assessment. These registry entries explain why the planned outcome reporting is absent; they do not indicate whether the intended comparison would have shown a difference. The planned enrollment total and any sample-size justification are not reported in the registry record.
The treatment comparison was observational. Eculizumab use was at the treating physician’s discretion, and there was no randomization. In general, treatment decisions in observational studies can be related to participant characteristics, disease history, or clinical circumstances. If those factors also relate to subsequent manifestations, a simple comparison of treatment and off-treatment periods may reflect those differences as well as treatment exposure. The registry record does not report an adjustment strategy or enough outcome data to assess such factors.
Secondary outcomes include change in estimated glomerular filtration rate from baseline to 24 months and incidence of plasma exchange and plasma infusion. Their titles alone do not provide results. No numerical estimates, uncertainty intervals, or analysis details for these outcomes are reported in the registry record. The fact that participants were also enrolled in M11-001 does not supply results for ECU-aHUS-403; the record says their data would be included in analyses for that other protocol.
The serious adverse event figures are descriptive counts by pediatric and adult groups, not a randomized safety comparison. The registry record does not establish that reported events were caused by eculizumab, nor does it provide a treatment-specific comparison or a clear observation period for those figures. Overall, the posted information supports describing the study’s design, intended outcomes, termination, and recorded adverse-event counts, but not a conclusion about comparative efficacy or safety.
9. Statistical Methods Explained
The registry record identifies this as a prospective, open-label study without participant randomization. In general, prospective studies define outcomes before or during follow-up and collect information as participants are observed. Open-label means treatment was not masked in the study description; the record does not report masking procedures for outcome assessment. Here, treatment was observational and at the discretion of the treating physician, so the study did not create randomized treatment groups.
What does an observational treatment comparison estimate?
In general, a randomized comparison uses assignment to balance measured and unmeasured characteristics across treatment groups on average. An observational comparison instead describes outcomes among participants or periods in which treatment occurred in clinical care. Treatment selection can be related to participant status or clinical events. Such differences can complicate interpretation, especially when the treatment and off-treatment periods are not directly comparable. The record itself cautions that the arms are not a like-for-like control comparison. It does not report a method to adjust for differences between periods or participants.
The endpoint compares a rate of TMA manifestations during eculizumab treatment with a rate off-treatment. For a rate, the event count is generally interpreted in relation to time at risk or exposure. In general, this makes the definition of the observation period and the handling of repeated events important. The registry record does not report the rate denominator, whether recurrent manifestations were counted, how treatment periods were defined, or which model was intended. No rate estimates or event counts are available for interpretation.
Why does the endpoint definition matter?
The registry definition encompasses hematologic or renal events due to aHUS, extra-renal clinical signs and symptoms of aHUS, and tissue biopsy demonstrating TMA due to aHUS. In general, a composite definition can bring several clinically distinct event types into a single outcome. It can also make event adjudication and consistent application of the definition important. The registry record does not report adjudication procedures, separate results by manifestation type, or how uncertain cases were handled.
How should uncertainty be read?
In general, a confidence interval expresses the range of effect estimates compatible with the observed data under the analysis assumptions. A narrow interval indicates greater statistical precision than a wide interval, while an interval that spans substantially different possibilities can leave the magnitude or direction uncertain. A significance test addresses compatibility with a specified null hypothesis under its assumptions; it does not by itself establish clinical importance or causation. For this study, the registry record reports no primary-outcome estimate, confidence interval, or test result. These measures therefore cannot be interpreted for the primary comparison.
Over-dispersion is a general issue in count data: it occurs when observed variability is greater than a model assumes. If a rate analysis uses a model that does not accommodate that extra variability, estimated uncertainty can be misleading. The registry record does not identify a model or say whether over-dispersion was assessed. It would be inappropriate to infer that a particular rate model, variance correction, or diagnostic was used.
What do planning illustrations mean?
In general, sample-size calculations describe the size of a study that might be needed under stated assumptions; they are not a measurement of the study’s observed statistical power. The stated planning framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event planning, the stated convention is a total number of events; other planning figures are participants per arm. These assumptions describe hypothetical planning illustrations, not the conduct of this nonrandomized study. The registry record does not report a sample-size justification for the trial itself. In addition, the primary outcome estimate needed to understand an observed effect is not available in the registry record, so the illustrations cannot substitute for an outcome analysis.
No analysis results are listed for this study. The registry record says that samples could not be analyzed to generate summary-level outcome data and that participants were concurrently enrolled in M11-001, where their data would be included in analyses. The analysis procedures for this study, including any covariate adjustment, handling of repeated observations, or sensitivity analyses, are not reported in the registry record. These omissions limit methodological assessment independently of the design’s observational nature.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary outcome and secondary outcomes, including change from baseline to 24 months in estimated glomerular filtration rate and incidence of plasma exchange and plasma infusion. It does not report how the analyses were to account for testing multiple outcomes or comparisons. In general, multiplicity matters because examining several outcomes can increase the chance of finding an apparently notable result by chance. A prespecified hierarchy or adjustment can help define how such results should be interpreted, but no such plan is reported in the registry record.
The registry record does not report a missing-data strategy, participant-level outcome completeness, or reasons for missing measurements. It specifically states that the collected samples for outcome assessment could not be analyzed to generate summary-level data after termination and loss of funding. This is more fundamental than a routine missing-value problem: the primary summary results are absent. The record does not describe whether any alternative data sources or analyses were used.
The primary population is described as all enrolled participants, but the registry record does not report analysis populations for the primary or secondary outcomes. It also does not report exclusions, follow-up completeness, or how participants who changed treatment status would be handled. In general, analysis-population definitions affect which participants contribute to an estimate and how an estimate should be understood. Without these details and without outcome summaries, the planned population cannot be matched to a completed analysis.
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 |
|---|---|---|---|
| Pediatric | 1 | 15 | 6.7% |
| Adult | 14 | 52 | 26.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pediatric | 0 of 15 |
| Adult | 0 of 52 |
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 |
|---|---|
| Pediatric | 6 of 15 |
| Adult | 31 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Pediatric | Adult |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 0 of 15 | 2 of 52 |
| Pyrexia | General disorders | 1 of 15 | 1 of 52 |
| Gastroenteritis | Infections and infestations | 0 of 15 | 2 of 52 |
| Gout | Metabolism and nutrition disorders | 0 of 15 | 2 of 52 |
| Headache | Nervous system disorders | 0 of 15 | 2 of 52 |
| Renal impairment | Renal and urinary disorders | 0 of 15 | 2 of 52 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 15 | 1 of 52 |
| Hyperparathyroidism | Endocrine disorders | 0 of 15 | 1 of 52 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 15 | 1 of 52 |
| Diverticulum | Gastrointestinal disorders | 0 of 15 | 1 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pediatric | Adult |
|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 1 of 15 | 11 of 52 |
| Nausea | Gastrointestinal disorders | 0 of 15 | 11 of 52 |
| Headache | Nervous system disorders | 1 of 15 | 10 of 52 |
| Diarrhoea | Gastrointestinal disorders | 0 of 15 | 7 of 52 |
| Asthenia | General disorders | 0 of 15 | 7 of 52 |
| Hypertension | Vascular disorders | 1 of 15 | 6 of 52 |
| Abdominal pain | Gastrointestinal disorders | 0 of 15 | 6 of 52 |
| Fatigue | General disorders | 0 of 15 | 6 of 52 |
| Blood creatinine increased | Investigations | 0 of 15 | 5 of 52 |
| Irritability | Psychiatric disorders | 0 of 15 | 5 of 52 |
Serious events with the highest arm-level rate: pyrexia (6.7%), influenza (6.7%), metapneumovirus infection (6.7%), viral infection (6.7%), anaemia (3.8%).
The registry lists pediatric and adult safety groups. In the pediatric group, 1 participant was recorded with a serious adverse event among 15 at risk; 6 were recorded with other adverse events among 15 at risk. In the adult group, 14 participants were recorded with a serious adverse event among 52 at risk; 31 were recorded with other adverse events among 52 at risk. Deaths were recorded as 0 in each group.
The listed serious adverse event terms and percentages are pyrexia, 6.7%; influenza, 6.7%; metapneumovirus infection, 6.7%; viral infection, 6.7%; anaemia, 3.8%; and gastroenteritis, 3.8%. These are descriptive entries, not evidence that eculizumab caused the events. The registry record does not give a treatment-specific safety contrast, event observation period, or detailed attribution information. The pediatric and adult counts should not be read as a randomized comparison, and the counts alone do not establish relative risk.
12. What the Result Does, and Does Not, Mean
The record establishes that a prospective, open-label study of aHUS was conducted, that treatment with eculizumab was left to treating physicians, and that the study was terminated after reaching only 20% of planned enrollment. It also records an intended comparison of TMA manifestation rates during treatment and off-treatment and provides a definition for those manifestations. These are meaningful details about the research question and its design.
The record does not provide the primary outcome results. It gives no TMA event totals or rates, no treatment-period comparison, and no uncertainty estimate. Thus, it cannot show whether manifestation rates were higher, lower, or similar during treatment and off-treatment. It cannot establish a causal treatment effect, and the observational design would require careful handling of differences associated with treatment decisions even if estimates were available.
The secondary outcome names do not establish changes in kidney function or the incidence of plasma exchange or plasma infusion. Likewise, the adverse-event counts describe recorded events by age group but do not establish causation or a comparative safety effect. The registry record does not report the details needed to assess duration of safety observation or treatment-specific attribution.
The record says that collected samples could not be analyzed for summary-level outcomes following termination and loss of funding. Participants were concurrently enrolled in M11-001, and the record states their data would be included in analyses for that protocol. That statement is not an outcome result for this study. The appropriate reading is therefore limited: the registry documents an intended clinical question, an observational design, a premature termination, and descriptive safety counts, but it does not answer the primary comparative outcome question.
13. Why This Trial Matters Statistically
This trial illustrates how a clear clinical question and a defined endpoint do not guarantee an interpretable treatment comparison. The study aimed to compare TMA manifestation rates during eculizumab treatment and off-treatment, but treatment was chosen by physicians rather than assigned randomly. In general, treatment selection and disease status can be intertwined in clinical care, so study design and analysis must address comparability before a difference in outcomes can be attributed to treatment.
It also demonstrates why outcome availability is essential to statistical interpretation. The record defines TMA manifestations across hematologic, renal, extra-renal, and tissue findings, yet reports that collected samples could not be analyzed to produce summary-level data. Without counts, rates, or uncertainty estimates, readers cannot assess the size or precision of the intended comparison. A planned outcome definition is not a substitute for an observed estimate.
Premature termination further distinguishes enrollment from an informative outcome analysis. The 67 enrolled participants represented 20% of planned enrollment, but those figures do not reveal how much information was available for a particular endpoint. The planned total, its justification, and the study’s intended statistical analysis are not reported in the registry record. Enrollment alone cannot establish whether the trial had adequate precision.
Finally, the record shows the value of separating descriptive safety reporting from comparative inference. Serious and other adverse events are listed by pediatric and adult group, but those counts do not create randomized comparisons or establish causation. Clear distinctions among design, outcome availability, precision, and descriptive safety data are necessary when interpreting an incomplete clinical trial record.
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 are specific to this study. It was terminated after only 20% of planned enrollment because program funding was subsequently lost. The record says that samples collected for outcome assessment could not be analyzed to generate summary-level data. This leaves the primary endpoint without a reported estimate and prevents evaluation of its precision or direction. The planned enrollment total and the rationale for that target are not reported in the registry record.
The treatment comparison was not randomized, and eculizumab use was at the treating physician’s discretion. The registry record cautions that the arms are not a like-for-like control comparison. It does not report how treatment periods were defined, how differences between participants or periods were addressed, or which statistical procedures were planned. Consequently, even if a descriptive contrast had been available, the record would not support treating that contrast as an unconfounded causal effect.
The study lists a baseline-to-24-month timeframe and secondary outcomes, but it does not report completeness of follow-up, outcome-specific denominators, missing-data handling, or analysis-population definitions. It does not describe event adjudication or provide results by TMA manifestation type. The adverse-event record is descriptive and does not specify a treatment-specific comparison or an observation period. Participants were also enrolled in M11-001, but the registry record does not provide the corresponding analyses or results there.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment — NCT02614898.
- Registry record last updated 2020-01-02; status last verified 2019-12.
- Results first posted 2020-01-02.
- 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
NCT02614898 evaluated potential predictors of disease progression in participants with atypical hemolytic uremic syndrome, including genetics, biomarkers, and treatment. Alexion Pharmaceuticals, Inc. was the sponsor. The prospective, open-label study enrolled 67 participants and was terminated. Its start date was 2015-11-04, and its primary completion date was 2017-10-05.
The primary outcome was the rate of TMA manifestations during eculizumab treatment compared with off-treatment, with a baseline and 24-month timeframe. Treatment was observational and at the treating physician’s discretion; participants were not randomized. The registry record states that enrollment reached only 20% of the planned total and that collected samples could not be analyzed to generate summary-level outcome data after program funding was lost. Participants were concurrently enrolled in M11-001, where their data would be included in analyses.