Multicenter Randomized Active-controlled Study to Investigate Efficacy & Safety of IV FCM in Pediatric Patients With IDA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter Randomized Active-controlled Study to Investigate Efficacy & Safety of IV FCM in Pediatric Patients With IDA (NCT03523117), a randomized phase 3 study. The primary outcome is Change in Hemoglobin g/dL.

2. Clinical Question

This is a randomized, active-controlled comparison rather than a comparison with no treatment. The registered objective refers to both efficacy and safety, but the primary endpoint described in the record is a continuous hemoglobin measure. The registry also lists changes in ferritin, TSAT, and reticulocyte hemoglobin content as secondary outcomes. The posted primary analysis reports a mean difference of 0.30 and a p-value of 0.311. These results describe the comparison under the recorded analysis; they do not, by themselves, establish that the groups are equivalent or that either treatment has a particular clinical effect.

3. Trial Design

The registry describes a completed, multicenter, randomized, active-controlled Phase 3 study with a parallel-group design. It enrolled 79 participants with iron deficiency anemia. The recorded start date is 2019-01-31, and the primary completion date is 2020-12-22. The registry lists ferric carboxymaltose and ferrous sulfate as the study interventions.

The two arms received different routes and schedules of iron treatment. Ferric carboxymaltose was given intravenously as two doses on day 0 and day 7, with the dose limited by the stated per-dose and total-dose maxima. Oral ferrous sulfate was described as a daily treatment over 28 days, with an age-dependent formulation and dosing approach. Full details of the oral regimen are not reported in the registry record. The IV administration description also does not give a complete infusion duration in the registry record.

Masking is listed as none, so the design is open-label. Randomization can help balance prognostic factors between groups on average, while an open-label design means treatment assignment was not masked as described in the registry. The record does not report the randomization sequence-generation method, concealment procedures, or any additional measures to limit bias.

The primary endpoint was change in hemoglobin from baseline to day 35. Its planned model was an ANCOVA including treatment group, baseline hemoglobin, and randomization strata defined by hemoglobin and age categories. The primary analysis population is identified as Intent to Treat. How that population was operationalized, including whether every randomized participant contributed to the primary analysis, is not reported in the registry record. Detailed sample-size justification and the trial's own design assumptions are 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.

Before assignment: Phase 3, multicenter, multinational, randomized, active-controlled study that compared the efficacy and safety of FCM to oral iron in pediatric participants with IDA and a documented history of an inadequate response to oral iron at least 8 weeks (56 days) prior to randomization. Participants who satisfied the inclusion requirements and no exclusionary criteria were eligible to participate in this study and enter into a screening phase to confirm eligibility.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT)

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 Change in Hemoglobin g/dL, measured over Baseline to day 35.

The primary endpoint is change in hemoglobin concentration, measured in g/dL, from baseline to day 35. Hemoglobin is a continuous laboratory measure, so the analysis describes the average change rather than counting participants who cross a threshold. The registry defines baseline hemoglobin as the last measurement obtained before randomization.

Change from baseline represents how the measured hemoglobin level differs between the baseline assessment and the day 35 assessment. Comparing changes can account for the fact that participants may begin with different hemoglobin values. The planned ANCOVA also includes baseline hemoglobin as a covariate, along with treatment group and the randomization strata based on hemoglobin and age categories.

In general, a continuous endpoint can preserve information about the magnitude of individual measurements rather than reducing them to categories. Hemoglobin is the primary measure in this trial because the registered primary objective concerns efficacy in pediatric participants with iron deficiency anemia. The registry lists the primary analysis population as Intent to Treat, but it does not report the endpoint's clinical threshold for an important change or how missing day 35 measurements were handled. The result therefore needs to be interpreted as an estimated group comparison in hemoglobin change, with its precision and analysis details in view, rather than as a direct statement about an individual participant's experience.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is described as a parametric analysis of covariance, or ANCOVA. In general, ANCOVA compares groups on a continuous outcome while adjusting for one or more covariates. Here, the outcome is change in hemoglobin from baseline to day 35, and the planned model includes treatment group, baseline hemoglobin, and the randomization strata based on hemoglobin and age categories. The registry identifies the analysis population as Intent to Treat.

What adjustment does

In general, adjustment accounts for measured variables that may be related to the outcome. Including baseline hemoglobin can make the treatment comparison conditional on starting hemoglobin rather than relying only on an unadjusted comparison of change. Including the randomization strata reflects the categories used in randomization. Adjustment does not guarantee that all relevant differences are removed, and it does not correct for variables that were not included in the model.

The registry defines baseline hemoglobin as the last measurement before randomization. This definition matters because a model needs a consistent rule for identifying the baseline value used in the analysis. The registry does not report further details about the model specification, such as additional covariates, diagnostics, or procedures for departures from model assumptions. Those details should not be inferred from the general description of ANCOVA.

How to read the reported means

The reported arm results are least-squares means, also called adjusted means in general statistical usage. They are model-based estimates rather than simple arithmetic averages. The ferric carboxymaltose estimate is 2.22 g/dL, with a 95% confidence interval from 1.69 to 2.75. The oral ferrous sulfate estimate is 1.92 g/dL, with a 95% confidence interval from 1.43 to 2.41. A confidence interval describes the uncertainty associated with an estimate under the model and its assumptions. It is not a range containing every participant's result.

The registry separately reports an ANCOVA mean difference of 0.30 and a p-value of 0.311. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that hypothesis and the analysis assumptions held. It does not measure the size or clinical importance of an effect, and it is not the probability that a result occurred by chance. The registry does not report a confidence interval for this between-arm estimate, limiting direct interpretation of its precision.

Why the analysis model matters

Model-based estimates depend on the model being appropriate for the data. In general, ANCOVA assumes a suitable relationship between the outcome and covariates and requires assumptions about the residuals and variance structure. The registry says the analysis is parametric but does not report diagnostic checks, transformations, or alternative models. It is therefore not possible to assess those details from the registry record.

The endpoint is continuous, and the registry identifies the outcome as a mean. In general, averages can be affected by extreme observations, and variability around an average is important for interpreting precision. The arm-level confidence intervals communicate some uncertainty in the adjusted means, but the registry does not report a standard deviation or a between-group confidence interval for the primary contrast. Dispersion details beyond the stated confidence intervals are not reported in the registry record.

Population, missingness, and multiplicity

Intent to Treat commonly refers to analyzing participants according to their randomized assignment, regardless of subsequent treatment received. That is a general definition; the registry names the ITT population but does not describe its precise implementation, the number included in the primary analysis, or how participants with missing outcome measurements were handled. Imputation methods, assumptions about missingness, and sensitivity analyses are not reported in the registry record.

The registry lists three secondary outcomes alongside the primary outcome, and records four outcome measures and four analyses. In general, testing multiple outcomes can increase the chance of at least one apparently notable result. Adjustment strategies, a testing hierarchy, and any multiplicity procedure are not reported in the registry record. The sample-size illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; it is explicitly a planning illustration based on the observed effect, not the trial's own design justification. It should not be interpreted as observed power.

Finally, the registry indicates no discrepancy between the posted result and the recalculation status. General recalculations based on summary data cannot reproduce every feature of a participant-level adjusted analysis. The sponsor-reported ANCOVA result is the relevant registered analysis, and unadjusted calculations should not be treated as a replacement for it.

10. Analyses Reported by the Sponsor

The registry reports the sponsor's comparison as an ANCOVA mean difference of 0.30, with a p-value of 0.311. The arm-level least-squares mean changes are 2.22 g/dL for ferric carboxymaltose and 1.92 g/dL for oral ferrous sulfate. The record does not report a confidence interval for the between-group estimate.

The primary analysis was adjusted for baseline hemoglobin, treatment group, and randomization strata based on hemoglobin and age categories. An unadjusted re-calculation from summary statistics would not necessarily reproduce that model-based comparison: it may not account for those covariates or the model's exact handling of the data. The registered ANCOVA result is therefore the relevant sponsor analysis for interpreting the primary endpoint. The record does not flag a discrepancy between the sponsor analysis and a recalculation.

The reported p-value should be read alongside the effect estimate and the missing contrast interval. It does not establish equivalence, and it does not state the probability that the treatments are the same. The registry describes the comparison as a superiority analysis, but the result should be interpreted through its reported estimate and uncertainty rather than the analysis label alone. No additional sponsor interpretation or explanation of the statistical result is reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary outcome as change in hemoglobin from baseline to day 35 and lists three secondary outcomes: change in ferritin, TSAT, and reticulocyte hemoglobin content. It records four outcome measures and four analyses. This indicates that more than one outcome was assessed, but the multiplicity strategy is not reported in the registry record. The record does not describe a hierarchy of hypotheses, an adjustment to significance levels, or whether secondary results were intended to support confirmatory conclusions.

In general, multiplicity matters because conducting several statistical tests can raise the chance of obtaining at least one result that appears notable under a chosen threshold. Whether and how to adjust depends on the trial's objectives and analysis plan. Without the registered strategy, the primary p-value can be read as the reported test for the primary endpoint, but claims based on a collection of outcomes cannot be assessed for family-wise error control.

The primary analysis population is named as Intent to Treat. The registry record does not report how many participants contributed outcome data to the primary analysis, whether all randomized participants were included, or how analysis populations were defined in practice. Missing-data handling, including imputation, assumptions about why data might be missing, and sensitivity analyses, is not reported in the registry record. This leaves uncertainty about how incomplete day 35 measurements, if any, would affect the estimates.

The record also does not report interim analyses, stopping rules, a detailed sample-size justification, or the full statistical analysis plan. These omissions do not show that such procedures were or were not used; they mean that these details cannot be evaluated from the registry record. The posted sample-size assumptions are described as planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are not observed power and are not evidence of the original trial's design rationale.

12. 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.

For serious adverse events, the registry records 0 affected participants among 40 at risk in the ferric carboxymaltose arm and 0 affected participants among 39 at risk in the oral ferrous sulfate arm. Deaths are recorded as 0 in both arms. The registry also records 0 participants with other adverse events in each arm. No serious adverse event terms are listed.

These are counts in the registry record, not proof that an event is impossible or that the treatments have identical safety profiles. In general, observing no events in a study does not rule out uncommon events, particularly when the number of participants is limited. The counts also describe the record's reported events; the record does not provide further details about adverse-event collection, follow-up completeness, severity categories beyond serious events, or causality assessment.

The safety figures should be interpreted separately from the primary hemoglobin analysis. Zero recorded serious events in both arms cannot establish comparative safety, and the registry does not report a statistical comparison of these counts. The data describe what was recorded for the enrolled groups during the trial as represented in the registry, not the full range of possible risks in other populations or settings.

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

The posted primary results estimate the mean change in hemoglobin through day 35 for each randomized group and report an adjusted comparison between the groups. The registry gives a least-squares mean change of 2.22 g/dL for ferric carboxymaltose and 1.92 g/dL for oral ferrous sulfate, with an ANCOVA mean difference of 0.30 and a p-value of 0.311. These statistics describe the registered endpoint and analysis; they do not provide a complete account of every outcome or participant experience.

The result does not establish that the treatments are equivalent. A p-value that does not provide strong evidence against a null hypothesis is not proof that the null is true. Demonstrating equivalence or noninferiority would ordinarily require a suitable design and prespecified margins, neither of which is reported in the registry record. Nor does the result establish that one treatment is clinically preferable. The registry does not report a threshold for a clinically important difference in hemoglobin change.

The result also does not answer questions about long-term outcomes, persistence of hemoglobin change, or outcomes beyond the measures and follow-up time listed in the record. The registry lists secondary laboratory outcomes, but their numerical results are not reported in the registry record, so they cannot be used to broaden the interpretation of the primary endpoint.

General statistical interpretation distinguishes an estimate from its uncertainty and from a clinical decision. The two arm-specific confidence intervals describe uncertainty around the adjusted means. The registry does not report a confidence interval for the between-arm contrast, so the precision of that contrast is not fully conveyed. The p-value alone cannot fill that gap.

Finally, these results arise from a randomized but open-label trial with 79 enrolled participants and limited registry detail about missing data, multiplicity, eligibility criteria, and the complete oral dosing regimen. These limitations shape how confidently the findings can be generalized. The record supports describing the observed model-based comparison, but not a broader conclusion about all pediatric patients with iron deficiency anemia or all treatment circumstances.

14. Why This Trial Matters Statistically

This trial offers a randomized active-controlled comparison of two iron treatments in pediatric participants with iron deficiency anemia. For statistical interpretation, that design is useful because it frames the primary question as a comparison between treatment groups rather than a change over time in a single group. The parallel design and recorded randomization provide the basis for the registered between-group analysis.

The primary endpoint is continuous and measured at a stated follow-up time: change in hemoglobin from baseline to day 35. The analysis uses ANCOVA and includes baseline hemoglobin and the randomization strata. This makes the distinction between adjusted estimates and simple group averages especially important. The reported least-squares means are model-based, while the registry's treatment comparison is the reported ANCOVA estimate.

The case also illustrates why a p-value is not a complete summary of evidence. The registry reports a mean difference and p-value, but no confidence interval for the between-group estimate. The arm-specific confidence intervals are useful for understanding uncertainty in each adjusted mean, but they do not directly supply the missing precision interval for the contrast. A result should therefore be read with attention to what the record reports and what it leaves unspecified.

Finally, this record highlights recurring reporting questions: how the Intent to Treat population was implemented, how missing measurements were handled, and whether multiple outcomes were controlled through a prespecified strategy. The registry does not report these details. Recognizing those gaps is part of sound statistical interpretation; it avoids treating a single numerical result as a complete account of the evidence.

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.

Several trial-specific limitations affect interpretation of the registered result. The study is listed as open-label, with no masking. The record does not describe procedures for limiting possible effects of unmasked treatment assignment on outcome assessment or other trial conduct. Randomization can support a fair comparison, but it does not remove every potential source of bias.

The total enrollment was 79, with 40 participants at risk for adverse events in the ferric carboxymaltose arm and 39 in the oral ferrous sulfate arm. The registry does not report the number of participants contributing data to the primary endpoint or the number with missing day 35 measurements. Missing-data methods and sensitivity analyses are not reported in the registry record. The population is described as pediatric participants with iron deficiency anemia, but detailed eligibility criteria and the age range are not reported.

The primary comparison has no reported confidence interval for the between-arm estimate. Although arm-specific least-squares means and confidence intervals are given, they do not replace an interval for the contrast. The registry also does not report the clinical importance threshold for hemoglobin change, limiting interpretation of the estimate's practical importance.

The registry describes the oral treatment as age-dependent and daily for 28 days, but the complete regimen is not reported in the registry record. The description of IV administration is also incomplete. The record does not provide a detailed statistical analysis plan, multiplicity procedures, interim analysis details, or the trial's sample-size justification. These omissions limit assessment of planned analyses and the completeness of reporting; they do not establish what procedures were or were not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multicenter Randomized Active-controlled Study to Investigate Efficacy & Safety of IV FCM in Pediatric Patients With IDA — NCT03523117.
• Registry record last updated 2022-06-22; status last verified 2022-05.
• Results first posted 2022-06-22.
• 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

NCT03523117 is a completed, randomized, open-label, parallel-group Phase 3 study comparing intravenous ferric carboxymaltose with oral ferrous sulfate in pediatric participants with iron deficiency anemia. The registry records enrollment of 79, a start date of 2019-01-31, and a primary completion date of 2020-12-22.

The primary endpoint was change in hemoglobin from baseline to day 35, analyzed using ANCOVA in the Intent to Treat population. Reported least-squares mean changes were 2.22 g/dL for ferric carboxymaltose and 1.92 g/dL for oral ferrous sulfate. The registry reports an ANCOVA mean difference of 0.30 and p-value of 0.311, without a confidence interval for the between-group estimate.

The registry records zero serious adverse events and zero deaths in both arms. It lists three secondary outcomes, but their numerical results and key details about missing-data handling, multiplicity, and the full statistical plan are not reported in the registry record.