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 A Phase III Safety Study of Ferumoxytol Compared to Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (IDA) (NCT02694978), a randomized phase 3 study. The primary outcome is Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02694978 |
| Phase | Phase 3 |
| Condition | Iron Deficiency Anemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2014 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AMAG Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned participants with iron deficiency anemia. The primary safety population included randomized participants who received any amount of study drug, with treatment group assigned according to the treatment actually received. The registry record does not give further eligibility details in the information available for this analysis.
Intervention
Participants received intravenous ferumoxytol. The brief summary describes a total dose of 1.020 grams. The treatment description specifies an infusion over at least 15 minutes and a second dose 7-8 days after the first dose, but the registry record’s detailed ferumoxytol description is truncated.
Comparator
The comparison was intravenous ferric carboxymaltose (FCM), with a total cumulative dose of 1.500 g. Its treatment description specifies an infusion over at least 15 minutes and a second dose 7-8 days after the first dose.
Primary question
The primary safety question was whether participants experienced treatment-emergent moderate to severe hypersensitivity reactions, including anaphylaxis, or moderate to severe hypotension from Day 1 after first dosing through Week 5. The endpoint combines these event types. A primary-endpoint result comparing the treatment groups is not reported in the registry record.
Because the primary endpoint is a composite, it concerns the occurrence of at least one event meeting the listed criteria rather than a single clinical event type. The description says potential signs and symptoms of hypersensitivity were recorded and adjudicated by a blinded Clinical Events Committee. Hypotension was defined using a decrease in systolic blood pressure. This framework makes the question one of safety events during a defined period after dosing, not a comparison of longer-term outcomes. The registry also lists secondary outcomes concerning moderate to severe hypersensitivity reactions, serious cardiovascular events and death, as well as changes in hemoglobin through Week 5. Numerical results for those secondary outcomes are not reported in the registry record.
3. Trial Design
This was a Phase III randomized, parallel-group trial. Its official title describes a multicenter, double-blind safety study; the registry classifies masking as quadruple. The planned comparison was between intravenous ferumoxytol and intravenous ferric carboxymaltose (FCM) in participants with iron deficiency anemia. The registry reports enrollment of 2014 and a completed status.
The treatment schedules involved two infusions. The FCM description specifies 750 mg in a final infusion volume of 250 mL, with a second dose 7-8 days after the first and a total cumulative dose of 1.500 g. The ferumoxytol description specifies 510 mg in a final infusion volume of 250 mL, with a second dose 7-8 days after the first; the detailed description is truncated before its total-dose statement. The brief summary gives the ferumoxytol total as 1.020 grams. Both descriptions specify infusions over at least 15 minutes.
The primary safety endpoint covers the period from Day 1 after first dosing through Week 5. Its analysis population included randomized participants who received any amount of study drug, and group assignment was based on actual treatment. This is a safety-population definition rather than a statement that every randomized participant was analyzed in the group originally assigned.
The registry reports a start date of 2016-02-29 and a primary completion date of 2017-01-16. Further details about the allocation procedure, the implementation of masking, the randomization ratio, the study sites, and participant eligibility criteria are not reported in the registry record. A protocol-level account of how the planned design was justified is also 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.
Overall Study
| Stage | Ferumoxytol | Ferric Carboxymaltose (FCM) |
|---|---|---|
| STARTED | 1006 | 1008 |
| Received at Least 1 Dose of Study Drug | 997 | 1000 |
| COMPLETED | 935 | 948 |
| NOT COMPLETED | 71 | 60 |
Reasons for not completing this period:
| Reason | Ferumoxytol | Ferric Carboxymaltose (FCM) |
|---|---|---|
| Adverse Event | 10 | 9 |
| Withdrawal by Subject | 22 | 19 |
| Lost to Follow-up | 14 | 17 |
| Death | 4 | 1 |
| Other-Decision of Participant | 6 | 1 |
| Other-Investigator's decision | 1 | 0 |
| Other-Unable to be reached | 0 | 1 |
| Other-Protocol noncompliant | 2 | 1 |
| Other-Personal reasons | 3 | 3 |
| Other-Withdrew prior to dosing | 9 | 8 |
Analysis population for the primary outcome, as defined in the registry: The safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
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 safety population included any randomized participant who received any amount of study drug. Treatment group was based on actual treatment.
| Characteristic | Unit | Ferumoxytol | Ferric Carboxymaltose (FCM) | Total |
|---|---|---|---|---|
| Participants analysed | 997 | 1000 | 1997 | |
| Age, Continuous | years | 55.6 (SD 17.30) | 54.8 (SD 17.02) | 55.2 (SD 17.16) |
| Sex: Female, Male: Female | Participants | 743 | 776 | 1519 |
| Sex: Female, Male: Male | Participants | 254 | 224 | 478 |
6. Primary Endpoint
The registry lists the primary outcome as Participants With Treatment-Emergent (TE) Moderate To Severe Hypersensitivity Reactions (Rxns), Including Anaphylaxis, Or Moderate To Severe Hypotension, measured over Day 1 (after first dosing) through Week 5.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with a treatment-emergent moderate to severe hypersensitivity reaction, including anaphylaxis, or moderate to severe hypotension. The stated observation window runs from Day 1 after first dosing through Week 5. Since the endpoint combines more than one event type, it summarizes whether a participant experienced an event meeting any of the specified criteria; it does not, by itself, show how many events belonged to each component.
The registry description notes that all intravenous iron formulations carry some risk of serious hypersensitivity reactions or anaphylaxis. Potential hypersensitivity signs and symptoms were recorded and adjudicated by a blinded Clinical Events Committee. Hypotension was defined as a >30% drop in systolic blood pressure from baseline or a decrease of >20 mmHg for systolic blood pressure. Those thresholds are part of the endpoint definition, not results.
As a general statistical point, a composite endpoint can capture several safety concerns in one outcome and can be useful when the study question concerns a broader category of events. Its interpretation depends on knowing both the overall composite result and the contributions of its components. The registry says statistical analysis was performed only on composite data. A numerical primary-endpoint comparison and component-specific primary results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a randomized comparison of two intravenous iron treatments and defines a safety endpoint for events observed through Week 5. It does not report a numerical result for the primary endpoint in the record available for this analysis. In particular, there is no posted primary-endpoint count by treatment group, effect estimate, confidence interval, or p-value to interpret. The registry notes that statistical analysis was performed only on composite data, but the composite result itself is not reported in the registry record.
The serious adverse-event information that is reported is separate from a primary-endpoint comparison. Among participants at risk, 36 of 997 in the ferumoxytol group and 35 of 1000 in the FCM group were recorded as having serious adverse events. For other non-serious adverse events, the counts were 186 of 997 and 245 of 1000, respectively. These are posted counts, not adjusted comparisons. The record does not provide a confidence interval or significance test for these figures. It also does not establish whether participants could appear in more than one adverse-event category or how event counts relate to the primary composite.
In general, a confidence interval describes the range of effect estimates compatible with the data and the statistical method used; its width reflects precision. Without an effect estimate and interval for the primary endpoint, the precision of a treatment-group contrast cannot be assessed from the registry record. A count in each group alone does not supply that missing comparison, and no new relative or absolute effect should be inferred from the posted counts.
The design was randomized, but the registry’s safety population included randomized participants who received any amount of study drug, assigned according to actual treatment. This means the reported population definition is based on treatment received. The registry record does not report how many randomized participants did not receive treatment or how missing outcome information was handled.
The appropriate reading is therefore limited: the record specifies the safety question and posts some adverse-event counts, but it does not give the primary composite result needed to judge the observed treatment-group contrast or its precision. No conclusion about the comparative safety effect can be drawn from an unreported primary-endpoint estimate.
9. Statistical Methods Explained
What kind of outcome is the primary endpoint?
The endpoint is binary at the participant level: a participant either meets the composite event definition during the specified period or does not. The registry describes it as a count of participants, and its definition includes treatment-emergent moderate to severe hypersensitivity reactions, including anaphylaxis, or moderate to severe hypotension. A participant-level count is not the same as a count of every event. If a person has more than one event, the composite definition may still count that person once, while event-level safety listings can capture multiple events. The registry record does not describe the event-counting conventions in greater detail.
As a general statistical explanation, binary outcomes are often summarized by the number of participants with an event and the number assessed in each group. A treatment contrast may then be expressed using an absolute difference or a relative measure. Those estimates require the relevant outcome counts and a specified analysis. The primary-endpoint counts and contrast are not reported in the registry record, so no such estimate can be interpreted for this endpoint.
Why combine different events?
General: a composite endpoint combines multiple outcomes into one prespecified category. This can provide a single summary when the study question concerns a group of related events. The resulting summary does not show whether the observed pattern is driven by one component or distributed across several. For that reason, component results can be important context. In this trial, the registry says the analysis was performed only on composite data; it does not report the primary composite counts or component-specific primary results.
Hypersensitivity and hypotension are not identical event types. The registry provides operational details for identifying hypotension and says potential hypersensitivity signs and symptoms were reviewed by a blinded Clinical Events Committee. Blinded adjudication is a process for reviewing whether reported events meet specified criteria without relying on knowledge of treatment assignment. The registry record does not report the adjudication charter, agreement between reviewers, or further details of the review process.
What does randomization contribute?
General: random assignment is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics at the start of a trial. That design feature supports a causal interpretation when the study is conducted and analyzed according to appropriate methods, but it does not remove uncertainty or guarantee balance in every realized sample. Here, the record identifies the trial as randomized and parallel-group. It does not report the randomization sequence method, allocation concealment procedure, or allocation ratio.
The analysis population is specifically described as randomized participants who received any amount of study drug. Treatment group was based on actual treatment. That is a safety-population rule. It differs from an analysis that retains every participant in the originally assigned group regardless of treatment received. The registry record does not report whether another analysis population was used for efficacy outcomes.
How should precision be assessed?
General: an estimate describes the observed contrast, while a confidence interval conveys its uncertainty under the statistical model and sampling assumptions. A narrow interval indicates greater precision than a wide interval, but neither interval alone determines clinical importance. A p-value, when reported, addresses compatibility with a specified null hypothesis under the analysis assumptions; it does not measure the size or importance of an effect. No primary-endpoint estimate, confidence interval, or p-value is reported in the registry record.
For binary outcomes, methods may use different assumptions about the outcome distribution and the way the treatment contrast is estimated. The registry record does not report the specific statistical model, covariate adjustments, confidence-interval method, or hypothesis-testing procedure for the primary endpoint. The statement that analysis was performed only on composite data does not identify those methods.
What are planning sample sizes?
General: a sample-size calculation is a planning exercise based on assumptions about the effect to be detected, variability or event frequency, significance level, power, allocation, and analysis method. A planning illustration based on an observed effect is not a design justification and is not observed power. It asks what sample size would be associated with a stated set of assumptions; it does not establish the probability that a completed trial has demonstrated an effect. The registry record does not report the trial’s own sample-size justification or the assumptions used to set enrollment.
The record describes an illustration using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. No calculated participant-per-arm figures are reported in the registry record. Such planning values, where presented, should be read as hypothetical planning quantities rather than trial outcomes.
Over-dispersion is a general concern when variation in count data exceeds what a simple statistical model assumes; accounting for it can affect standard errors and uncertainty estimates. It is not established as a feature of this participant-level binary endpoint, and the registry record does not report a model that would permit assessing it.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes including participants with moderate to severe hypersensitivity reactions, serious cardiovascular events, and death; mean change in hemoglobin from baseline to Week 5; and mean change in hemoglobin per gram of iron administered from baseline to Week 5. The registry record does not describe a multiplicity strategy for interpreting tests across the primary and secondary outcomes. It does not state whether outcomes were arranged in a testing hierarchy, whether any adjustment was planned, or which result would be considered confirmatory.
Multiplicity is a general issue when several hypotheses are tested: the chance of at least one apparently notable result can increase as the number of tests grows, depending on their relationships and the testing approach. This does not mean that every reported result is invalid; it means interpretation depends on a prespecified analysis plan and transparent reporting. The statistical plan and any interim analyses are not reported in the registry record.
The primary safety population is described as randomized participants who received any amount of study drug, grouped according to actual treatment. The registry record does not report the amount or pattern of missing primary-endpoint data, how missingness was handled, or whether sensitivity analyses were performed. It also does not report a participant flow accounting for exclusions from the safety population.
These omissions limit assessment of the analysis population and the robustness of any treatment comparison. They do not demonstrate that missing data or multiplicity affected the results; rather, the relevant procedures and primary-endpoint result are not reported in the registry record.
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 |
|---|---|---|---|
| Ferumoxytol | 36 | 997 | 3.6% |
| Ferric Carboxymaltose (FCM) | 35 | 1000 | 3.5% |
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 |
|---|---|
| Ferumoxytol | 186 of 997 |
| Ferric Carboxymaltose (FCM) | 245 of 1000 |
Most frequent serious adverse event terms
| Event term | Organ system | Ferumoxytol | Ferric Carboxymaltose (FCM) |
|---|---|---|---|
| Syncope | Nervous system disorders | 3 of 997 | 3 of 1000 |
| Gastroenteritis | Infections and infestations | 3 of 997 | 1 of 1000 |
| Cardiac failure congestive | Cardiac disorders | 1 of 997 | 3 of 1000 |
| Seizure | Nervous system disorders | 2 of 997 | 0 of 1000 |
| Pneumonia | Infections and infestations | 2 of 997 | 0 of 1000 |
| Haemorrhagic anaemia | Blood and lymphatic system disorders | 2 of 997 | 0 of 1000 |
| Acute kidney injury | Renal and urinary disorders | 2 of 997 | 0 of 1000 |
| Gastric ulcer haemorrhage | Gastrointestinal disorders | 1 of 997 | 1 of 1000 |
| Cellulitis | Infections and infestations | 1 of 997 | 1 of 1000 |
| Fluid overload | Metabolism and nutrition disorders | 1 of 997 | 1 of 1000 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ferumoxytol | Ferric Carboxymaltose (FCM) |
|---|---|---|---|
| Headache | Nervous system disorders | 60 of 997 | 82 of 1000 |
| Nausea | Gastrointestinal disorders | 35 of 997 | 60 of 1000 |
| Fatigue | General disorders | 30 of 997 | 36 of 1000 |
| Dizziness | Nervous system disorders | 25 of 997 | 40 of 1000 |
| Diarrhoea | Gastrointestinal disorders | 29 of 997 | 33 of 1000 |
| Abdominal pain | Gastrointestinal disorders | 17 of 997 | 21 of 1000 |
| Back pain | Musculoskeletal and connective tissue disorders | 19 of 997 | 16 of 1000 |
| Pyrexia | General disorders | 7 of 997 | 22 of 1000 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 11 of 997 | 18 of 1000 |
| Cough | Respiratory, thoracic and mediastinal disorders | 15 of 997 | 13 of 1000 |
Serious events with the highest arm-level rate: syncope (0.3%), gastroenteritis (0.3%), cardiac failure congestive (0.3%), seizure (0.2%), pneumonia (0.2%).
The posted serious adverse-event counts are 36 of 997 participants at risk in the ferumoxytol group and 35 of 1000 participants at risk in the ferric carboxymaltose (FCM) group. For other non-serious adverse events, the counts are 186 of 997 and 245 of 1000, respectively. These figures describe participants recorded with events in the posted safety information. They are not the primary composite endpoint result.
The registry also lists serious adverse-event terms with percentages, including syncope, gastroenteritis, congestive cardiac failure, seizure, pneumonia, and haemorrhagic anaemia. Those listings do not replace an overall treatment comparison or provide a causal assessment for each event. The registry record does not report a statistical comparison, confidence interval, or p-value for the serious and other non-serious adverse-event counts. The number of deaths is not reported in the adverse-event group information.
As a general reading principle, adverse-event counts should be interpreted alongside their denominators, definitions, observation periods, and rules for attributing events. The registry record’s primary endpoint has its own definition and timeframe, and the serious adverse-event summary should not be treated as if it were the result for that endpoint. The record does not report whether participants could contribute to more than one listed event category.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized Phase III trial compared intravenous ferumoxytol with intravenous ferric carboxymaltose in participants with iron deficiency anemia, and that its primary safety question concerned a composite of moderate to severe hypersensitivity reactions, including anaphylaxis, or moderate to severe hypotension through Week 5. It also describes how the safety population was defined and posts selected adverse-event counts.
What the record does not establish is the size or precision of the primary treatment-group contrast. No primary-endpoint event counts, effect estimate, confidence interval, or p-value are reported in the registry record. Therefore, the posted information cannot support a numerical statement about how the treatments compared on the primary composite, nor can it show how much uncertainty surrounds such a comparison.
The serious adverse-event counts and other non-serious adverse-event counts are descriptive information. Without a reported analysis and its uncertainty, the counts alone do not show whether a difference between groups is distinguishable from chance variation. They also should not be substituted for the specifically defined primary endpoint. A count of participants with serious adverse events is not necessarily equivalent to a count meeting the composite endpoint criteria.
General: absence of a reported result is not evidence that the groups were identical, and it is not evidence that they differed. It means the relevant estimate cannot be assessed from the registry record. Likewise, no unreported analysis plan, sample-size rationale, or missing-data method can be inferred from the trial’s design label or enrollment.
The findings that can be described are the trial’s design, endpoint definition, population rule, and posted safety counts. Claims about comparative safety, statistical significance, or the practical importance of a difference require results and methods that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates a recurring statistical challenge in safety studies: the primary question can combine several types of events while the posted information may not include the outcome counts or analysis needed to interpret the comparison. Here, the endpoint covers moderate to severe hypersensitivity reactions, including anaphylaxis, or moderate to severe hypotension. A composite can summarize a broader safety category, but a numerical result and clear information about its components are important for understanding what the composite represents.
The record also distinguishes the primary composite from the broader adverse-event summaries. Serious and other non-serious adverse-event counts can provide useful descriptive context, but they answer different questions from the defined primary endpoint unless their definitions and analyses match. Keeping these outcomes separate prevents a descriptive count from being mistaken for the main treatment comparison.
Another statistical issue is the analysis population. The safety population included randomized participants who received any amount of study drug, and assignment was based on actual treatment. That definition matters because an analysis population determines which participants contribute to a result and how they are grouped. The record does not provide enough detail to assess the effect of this rule or compare it with other possible analysis populations.
Finally, enrollment and randomization do not by themselves establish the precision of a result. Precision is assessed through reported estimates and uncertainty intervals, and interpretation also depends on the analysis plan, missing-data handling, and treatment of multiple outcomes. Those details and the primary-endpoint estimate are not reported in the registry record. This example shows why a complete statistical reading requires the result as well as the design and endpoint definition.
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 most important limitation for statistical interpretation is that the registry record does not report the primary composite endpoint result. It defines the endpoint and says analysis was performed only on composite data, but does not give group-specific primary counts, an effect estimate, a confidence interval, or a p-value. This prevents assessment of the observed contrast and its precision.
The registry’s description of the ferumoxytol arm is truncated before its detailed total-dose statement, although the brief summary gives a total of 1.020 grams. The FCM description gives a total cumulative dose of 1.500 g. Further details about participant eligibility, the randomization procedure, the allocation ratio, and the statistical model are not reported in the registry record.
The safety population was based on receiving any amount of study drug, with participants grouped by actual treatment. The record does not report the numbers randomized by group, the number who did not receive treatment, or a complete account of participants included in each outcome analysis. Missing-data handling and sensitivity analyses are also not reported in the registry record.
Some serious and other non-serious adverse-event counts are posted, but the record does not provide uncertainty estimates or statistical comparisons for those counts. It also does not report the number of deaths in the adverse-event group information. The listed secondary outcomes lack numerical results in the registry information available for this analysis.
The protocol-level sample-size justification, interim-analysis procedures, multiplicity approach, and detailed statistical analysis plan are not reported in the registry record. These omissions limit independent assessment of planned inference and robustness; they do not, on their own, show that the trial’s methods were inappropriate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase III Safety Study of Ferumoxytol Compared to Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (IDA) — NCT02694978.
- Registry record last updated 2023-07-25; status last verified 2023-07.
- Results first posted 2018-06-11.
- 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
NCT02694978 is a completed Phase III randomized, parallel-group safety study of intravenous ferumoxytol versus intravenous ferric carboxymaltose (FCM) for iron deficiency anemia. The official title describes a multicenter, double-blind study, and the registry classifies masking as quadruple. Enrollment was 2014.
The primary endpoint counted participants with treatment-emergent moderate to severe hypersensitivity reactions, including anaphylaxis, or moderate to severe hypotension from Day 1 after first dosing through Week 5. The safety population included randomized participants who received any amount of study drug, grouped by actual treatment. A numerical primary-endpoint comparison is not reported in the registry record.
Posted adverse-event counts include serious events in 36 of 997 ferumoxytol participants and 35 of 1000 FCM participants, and other non-serious events in 186 of 997 and 245 of 1000, respectively. The registry record does not report statistical comparisons or uncertainty estimates for these counts.