Compare Efficacy/Safety of Repeat Doses of Ferumoxytol With Iron Sucrose in CKD Subjects With IDA and on Hemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Compare Efficacy/Safety of Repeat Doses of Ferumoxytol With Iron Sucrose in CKD Subjects With IDA and on Hemodialysis (NCT01227616), a randomized phase 4 study. The primary outcome is Hemoglobin Changes.

2. Clinical Question

The trial addresses a treatment comparison in a defined clinical setting: iron deficiency anemia among people whose chronic kidney disease requires hemodialysis. Its stated objectives include comparing efficacy and safety for repeated intravenous ferumoxytol doses and intravenous iron sucrose. The primary endpoint focuses on hemoglobin, a continuous measurement, and assesses change over the period from baseline to Week 5.

The comparison is randomized and uses parallel groups. It is not described as a crossover comparison in which every participant receives both treatments. The registry record identifies no masking; the trial is open-label. These features matter when interpreting the question: random allocation is intended to support a fair comparison of assigned groups, while open-label treatment means participants and study personnel were not masked to assignment.

The registry also lists changes in transferrin saturation and the proportion of subjects with a hemoglobin increase of at least 1.0 g/dL at any time from treatment-period baseline to Week 5 for each treatment period as secondary outcomes. Those outcomes complement, but do not replace, the stated primary question about mean hemoglobin change. Numerical results for the primary and secondary outcomes are not reported in the registry record.

3. Trial Design

The record identifies this as a Phase IV, randomized, open-label, multicenter, parallel-group trial. It compares repeated intravenous ferumoxytol with intravenous iron sucrose in people with iron deficiency anemia and hemodialysis-dependent chronic kidney disease. The registry lists enrollment of 296. That figure is the registered enrollment, not a report of how many participants completed treatment or contributed data to a particular analysis.

Random allocation assigns participants to treatment groups according to a chance-based process. In general, randomization can reduce systematic differences between groups at the start of a trial, although it does not guarantee that every characteristic will be balanced. The registry record does not report details of the allocation sequence, concealment procedures, or stratification, so those aspects cannot be assessed from the record.

The parallel design means the groups are compared alongside one another rather than being described as a sequence in which each participant receives both treatments. The record says the study had no masking and was open-label. This can be relevant to care decisions, behavior, and judgments about outcomes, although hemoglobin is a measured laboratory outcome. The registry record does not describe procedures for laboratory measurement or whether laboratory personnel were masked.

The primary outcome timeframe is up to 6 treatment periods, with 5 weeks per treatment period. The outcome description compares mean hemoglobin between baseline and Week 5 for ferumoxytol and iron sucrose in each period. The record also identifies an MRI substudy in the official title, but the details and results of that substudy are not reported in the registry record.

The listed study dates are a start in 2013-08 and primary completion in 2016-02; the status is completed. These administrative details do not establish how many participants had evaluable endpoint data, how much follow-up was achieved, or whether every planned treatment period was completed. Those details are 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: A total of 296 hemodialysis patients with IDA who met the entry criteria were enrolled and randomized (ferumoxytol: n=197; iron sucrose: n=99). One subject in the ferumoxytol group and 2 subjects in the iron sucrose group withdrew prior to receiving study drug, resulting in 293 total participants for analysis.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Mean Change in Hemoglobin at Week 5 - ITT Population

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.

6. Primary Endpoint

The registry lists the primary outcome as Hemoglobin Changes, measured over Up to 6 treatment periods (5 weeks per treatment period).

The primary endpoint is mean change in hemoglobin, measured in g/dL, from baseline to Week 5. The registry describes the comparison for ferumoxytol and iron sucrose in each treatment period, over up to 6 treatment periods of 5 weeks each. The listed analysis population is the ITT population. The outcome is described as a mean, with standard deviation as the dispersion measure.

Hemoglobin is a continuous measure. Examining change from baseline focuses on how the measurement shifts during a treatment period, rather than comparing only a follow-up value without reference to where participants began. A mean change describes the average change in the analyzed group; it does not indicate that every participant changed by that amount. The standard deviation describes variability among individual measurements or changes around the mean, rather than the precision of the estimated mean.

This endpoint is useful for a treatment comparison because it expresses change on a common clinical measurement scale. The Week 5 time point gives the comparison a defined interval within each treatment period. The registry record does not report the actual mean changes, standard deviations, participant counts contributing to each period, or an estimated between-group contrast. It therefore does not permit assessment of the size or precision of the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary endpoint is a continuous outcome: change in hemoglobin from baseline to Week 5. A group mean summarizes the average change among the participants included in an analysis. It does not imply that every participant experienced the average change, and it can obscure variation in individual responses. The registry identifies standard deviation as the measure of dispersion. In general, standard deviation describes how spread out observations are around their mean; it is not the same as a confidence interval for the mean.

Comparing changes from baseline can make the treatment contrast easier to interpret as change during the treatment period. A comparison of group means is still affected by the analysis choices, including the handling of repeated measurements, missing observations, and the population included. The registry record does not give the numerical means or standard deviations, or enough analysis detail to evaluate those choices.

What would a between-group estimate and confidence interval add?

A between-group estimate would quantify the average separation in hemoglobin change for the treatments on the stated measurement scale. A confidence interval would communicate the uncertainty around that estimate. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The interval also helps readers consider which effect sizes remain compatible with the data, rather than relying only on whether a threshold for statistical significance was crossed.

Neither a confidence interval nor a p-value for the primary contrast is reported in the registry record. It is therefore not possible to describe the precision of the estimated treatment difference or to characterize a test of a null hypothesis. No effect estimate should be inferred from the design description alone.

Why does the repeated-period structure matter?

The primary outcome is described for each treatment period, with up to 6 treatment periods and 5 weeks per period. Repeated measurements from the same participant are generally related; they should not automatically be treated as independent observations. General methods for repeated data can account for within-participant dependence and period structure. The choice of method affects how uncertainty is estimated and what treatment effect is being summarized.

The registry record does not report whether the analysis used a repeated-measures model, separate period-specific comparisons, or another approach. It does not describe period effects, carryover considerations, or how participants with incomplete treatment periods were handled. Those details cannot be reconstructed from the endpoint description. The parallel-group design does not, by itself, identify the statistical model used for repeated outcome measurements.

How should over-dispersion be understood?

Over-dispersion is a general issue for count or binary outcomes when observed variability exceeds what a chosen statistical model expects. It can lead to uncertainty estimates that are too small if the model does not account for that extra variation. It is not a feature that can be diagnosed from the continuous primary endpoint description alone. The registry record does not report a model or diagnostic assessment for over-dispersion.

For a binary secondary outcome, such as whether a participant reached a specified hemoglobin increase, an analysis would need to define the denominator and account for the repeated treatment-period observations if applicable. The registry record does not provide those analysis details or the outcome results. For event counts, exposure time and recurrent events may also matter, but these are not described for the posted adverse-event figures.

What do the planning illustrations mean?

Sample-size calculations associated with observed effects are planning illustrations, not observed power. In general, an illustration asks how many participants might be needed under specified assumptions to detect an effect of a chosen size. The assumptions described for these illustrations include a two-sided significance level of 0.05, equal allocation between the groups, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. These are not evidence that the trial was designed using those assumptions.

The registry record does not report the trial’s own sample-size justification or protocol-level power calculation. The listed enrollment is not itself a sample-size rationale, and the planning illustrations should not be read as a measure of the probability that the completed trial found a particular result. Any sample-size figures are prospective planning aids under their stated assumptions, not a substitute for observed estimates and their uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome spans repeated treatment periods, and the registry lists secondary outcomes as well. When several outcomes, time points, or comparisons are examined, there is a general risk of finding apparently notable results by chance. Statistical plans can address multiplicity by identifying a primary comparison, adjusting inference, or describing results as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which analyses were prespecified beyond identifying the primary outcome.

The record does not report how missing hemoglobin measurements or incomplete treatment periods were handled. It also does not describe imputation, exclusion rules, sensitivity analyses, or the amount and pattern of missing data. These details matter because an analysis based only on participants with observed measurements can be affected if the availability of measurements is related to outcomes or treatment experience.

The primary outcome population is identified as ITT. In general, intention-to-treat analysis aims to retain participants in the groups to which they were randomized, regardless of treatment adherence. The registry record does not provide enough detail to establish how that principle was implemented for repeated periods, participants with missing measurements, or participants who did not contribute an endpoint value. The actual analysis population size is not reported in the registry record.

Accordingly, neither the impact of missing data nor the handling of multiple period-specific and secondary comparisons can be assessed from the registry record. These are limits on judging the reliability and scope of any treatment inference, especially when the numerical outcome results and full statistical plan are also not reported.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infections and infestations (19.4%), injury, poisoning and procedural complications (16.5%), cardiac disorders (15.5%), vascular disorders (13.4%), gastrointestinal disorders (12.8%).

The registry lists serious adverse events and other adverse events by treatment group, along with deaths. For ferumoxytol, 196 participants are listed as at risk for serious adverse events, with 93 affected; 196 are listed as at risk for other adverse events, with 158 affected; and 16 deaths are listed. For iron sucrose, 97 are listed as at risk for serious adverse events, with 49 affected; 97 are listed as at risk for other adverse events, with 81 affected; and 6 deaths are listed. These are the registry’s group-specific counts, not a statistical comparison.

The record lists the leading serious-event categories with percentages: infections and infestations, 19.4%; injury, poisoning and procedural complications, 16.5%; cardiac disorders, 15.5%; vascular disorders, 13.4%; gastrointestinal disorders, 12.8%; and respiratory, thoracic and mediastinal disorders, 10.7%. The denominator and method used for these percentages are not reported in the registry record, so they should not be interpreted as group-specific risks.

Counts of affected participants do not show when events occurred, how long participants were observed, or whether participants experienced more than one event. The registry record does not report a comparative safety analysis or exposure-adjusted rates. The figures are therefore descriptive and do not establish that one treatment caused more or fewer events than the other.

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

The registry record establishes that a randomized, open-label, parallel-group trial compared repeated intravenous ferumoxytol with intravenous iron sucrose for iron deficiency anemia in people with hemodialysis-dependent chronic kidney disease. It identifies mean change in hemoglobin from baseline to Week 5 as the primary endpoint and specifies an ITT population. It also describes secondary outcomes and group-specific safety counts.

What the record does not establish is the observed size or direction of the primary treatment contrast. Numerical mean changes, variability estimates, a between-group estimate, confidence intervals, and p-values are not reported in the registry record. Without these, the efficacy result cannot be characterized as favoring either group, as precise or imprecise, or as statistically distinguishable from a null difference. The absence of these numbers should not be mistaken for a finding of no difference.

The safety information also has limits. The posted counts describe affected participants and deaths by group, but do not provide a comparative analysis, event timing, exposure-adjusted rates, or the basis for the listed serious-event percentages. The counts can be read as recorded descriptive information, not as a causal estimate or a basis for concluding that one treatment is safer.

General statistical interpretation requires attention to both effect size and uncertainty. A treatment contrast may be estimated with considerable or limited precision, and a confidence interval would help readers understand that uncertainty. Statistical significance alone, if it were available, would not determine clinical importance. The record does not report the quantities needed to make those judgments.

The study’s findings also cannot be generalized beyond the population and setting described without additional evidence. The trial concerns people with hemodialysis-dependent chronic kidney disease and iron deficiency anemia, uses an open-label design, and includes repeated treatment periods. The registry record does not provide detailed information about participant characteristics, adherence, missing outcomes, or analysis methods. Those omissions constrain assessment of applicability as well as internal validity.

13. Why This Trial Matters Statistically

This trial is statistically notable for the structure of its primary outcome. The endpoint is not simply a single follow-up measurement: it is change from baseline to Week 5, described across up to 6 treatment periods. That structure raises questions about how period-specific observations were summarized, how within-participant correlation was handled, and whether the intended treatment contrast was consistent across periods. Those choices are important to the estimate and its uncertainty.

The design also illustrates the distinction between a registered trial question and a reported result. Randomization, the treatment groups, the endpoint, and the listed analysis population describe what was intended to be compared. They do not supply the numerical outcome estimates. Without those estimates, readers cannot judge effect magnitude or precision, even though the registry record identifies the study as completed.

Safety reporting illustrates another statistical distinction: counts are not rates, and descriptive counts are not adjusted comparisons. The record provides group-specific counts at risk and affected, plus deaths, but does not provide timing, person-time, or a comparative model. This limits what can be concluded from the figures, particularly when follow-up or exposure may differ.

Finally, the record does not state the trial’s own sample-size justification, missing-data approach, multiplicity strategy, or detailed statistical plan. These omissions matter because repeated measures and multiple outcomes can influence inference. The case underscores why a clear protocol and complete outcome reporting are needed to evaluate not only whether groups differ, but also how large and how precisely estimated any difference is.

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 largest limitation for interpreting efficacy is that numerical primary-outcome results are not reported in the registry record. Although the endpoint and its timeframe are described, the record gives no group mean changes, standard deviations, treatment contrast, confidence interval, or p-value. The results for the listed secondary outcomes are also not reported. Consequently, no assessment of the primary effect’s magnitude, direction, or precision is possible from this record.

The endpoint’s repeated-period structure is described, but the analysis method is not. The registry record does not explain whether period-specific results were analyzed separately or combined, how correlations among repeated observations were addressed, or how incomplete periods were handled. It also does not report missing-data methods, sensitivity analyses, multiplicity procedures, or the trial’s own statistical analysis plan.

Although the primary population is labeled ITT, the registry record does not give the number analyzed or specify how the ITT principle was applied when measurements were missing or participants did not complete treatment periods. Enrollment of 296 does not establish the number with usable primary endpoint data.

The design is open-label, and the record does not describe masking of outcome assessors or laboratory personnel. The outcome is a laboratory measure, but the record does not provide measurement procedures or quality-control details. Safety reporting is descriptive and lacks event timing, exposure-adjusted analyses, and the denominator underlying the listed serious-event percentages. The MRI substudy is named, but its methods and findings are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Compare Efficacy/Safety of Repeat Doses of Ferumoxytol With Iron Sucrose in CKD Subjects With IDA and on Hemodialysis — NCT01227616.
• Registry record last updated 2022-04-21; status last verified 2022-03.
• Results first posted 2019-07-19.
• 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.

18. Record Summary

The registry record describes a completed Phase IV, randomized, open-label, multicenter, parallel-group trial of repeated intravenous ferumoxytol compared with intravenous iron sucrose. The population is people with iron deficiency anemia and hemodialysis-dependent chronic kidney disease; listed enrollment is 296. The primary outcome is mean hemoglobin change from baseline to Week 5 in the ITT population, assessed across up to 6 treatment periods, with 5 weeks per period.

Secondary outcomes include changes in transferrin saturation and the proportion with a hemoglobin increase of at least 1.0 g/dL during a treatment period. The registry also lists group-specific serious and other adverse-event counts and deaths. Numerical primary and secondary efficacy results, a comparative safety analysis, and key analysis details—including missing-data and multiplicity methods—are not reported in the registry record.