Efficacy of Enteral Iron Supplementation in Critical Illness: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Enteral Iron Supplementation in Critical Illness (NCT00450177), a randomized phase 2 study. The primary outcome is Hematocrit.

2. Clinical Question

The study’s stated purpose was to investigate whether enteral iron supplementation could improve anemia, decrease the risk of blood transfusion and decrease mortality among patients hospitalized in an intensive care unit. It also aimed to address a possible relationship between enteral iron and infection risk. These are the research aims, not conclusions about what the trial found. Although the registry lists the clinical questions and outcome time points, primary outcome results are not reported in the registry record. The available record therefore does not establish the direction, size or precision of any hematocrit difference between groups.

3. Trial Design

The registry describes a Phase 2, randomized, parallel-group, placebo-controlled trial. Its masking designation is quadruple. That label indicates the registry’s recorded masking category; the specific people who were masked and the procedures used to maintain masking are not reported in the registry record. The sponsor was Weill Medical College of Cornell University.

The study began in 2006-01, and primary completion was recorded as 2007-12. Its status is completed. The registry lists enrollment of 200, but it does not describe the number assigned to each arm in the main trial record. The adverse-event entries use their own at-risk counts; these should not be treated as a complete accounting of allocation or primary-outcome observations.

Participants in the iron group were assigned ferrous sulfate 325 mg by capsule or oral solution, with doses scheduled three times a day at 9 am, 1pm and 5 pm. Participants in the placebo group were assigned a placebo capsule on the same schedule. Treatment in either group was to continue until hospital discharge or for 42 days, whichever occurred first. Details such as adherence, treatment interruptions and the precise procedures for administering the oral solution are not reported in the registry record.

The trial’s focus was broader than hematocrit alone. The secondary outcomes listed include receipt of at least one RBC transfusion, at least one infection, drug-related constipation, average days taking antibiotics, hospital mortality and average length of hospital stay. The registry lists 10 outcome measures and 1 analysis, but does not provide enough detail to determine how every outcome was operationalized or analyzed. A completed status describes the trial’s status in the registry, not whether its planned outcomes were reported.

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

Reasons for not completing this period:

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 Hematocrit, measured over Day 7, Day 14, Day 21, Day 28.

Hematocrit is the percentage of blood volume occupied by red blood cells. It is a continuous measure, and the registry specifies that the primary result is to be expressed as a mean with standard deviation. The record lists measurements at Day 7, Day 14, Day 21 and Day 28. It does not give a primary-outcome description beyond the measure, unit and time points, and the population for this endpoint is not specified in the outcome entry.

As a general statistical matter, a continuous measure can preserve information about the range of observed values rather than reducing observations to categories. A group mean describes the center of the observed measurements, while a standard deviation describes their spread. Comparing means can therefore address whether the groups’ measured hematocrit levels differ on average, but interpretation also depends on the estimated difference, its uncertainty, the time point and the analysis population.

Hematocrit is relevant to the stated aim of investigating anemia. However, a measurement at a listed time point is not by itself evidence of a treatment effect. The record does not report group means, standard deviations, between-group estimates, confidence intervals or tests for any of the listed days. The primary outcome has several time points and was not reduced to one comparison in the posted result information. Consequently, the magnitude and precision of the hematocrit findings cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary measure as continuous and specifies a mean with standard deviation. In general, a mean represents the average measured value in a group, while the standard deviation describes the spread of individual values around that average. These summaries are descriptive. A comparison between groups requires an estimate of the contrast and an approach to quantify its uncertainty. The registry record does not report those primary-outcome results or identify the model used to estimate them.

The hematocrit outcome is listed at Day 7, Day 14, Day 21 and Day 28. In general, measurements from the same participant over time may be related rather than independent. An analysis that uses repeated measurements may need to account for that relationship; alternatively, an analysis may compare groups separately at particular time points. The registry does not report which approach was used, whether the primary analysis focused on one time point, or how results across the listed times were combined. It would not be appropriate to infer a repeated-measures model, a particular comparison or a primary time point from the list alone.

Randomization is a design method intended to support comparison between assigned groups by limiting systematic differences at allocation. Its value for interpretation depends on conduct and analysis as well as assignment. The record labels the trial randomized but does not report the sequence-generation method, allocation-concealment procedures, stratification factors, or how departures from assigned treatment were handled. The parallel-group designation indicates that participants were assigned to a group for comparison; additional details of the design are not reported.

The registry describes masking as quadruple. Masking can, in general, reduce the risk that knowledge of assignment influences care, assessment or reporting. The record does not identify which roles were masked, how masking was maintained, or whether masking was assessed. The presence of a placebo comparator and a masking label should not be taken as a complete account of these procedures.

The record includes a planning-illustration assumption: two-sided significance level 0.05, equal allocation between the two arms and a normal approximation. It describes the target effect as a stated share of the observed effect. These assumptions concern a planning illustration, not the trial’s own documented design justification. The record does not report the sample-size justification used by the investigators, nor does it report the numerical outputs of a planning calculation in the information available for interpretation. Planning sample sizes, when reported, are illustrations and not observed power. Observed power is not a substitute for an estimated effect and its uncertainty.

General statistical interpretation would usually consider the estimated between-group difference alongside a confidence interval and, where relevant, a test result. A p-value, if reported, would describe how unusual data at least as incompatible with a specified null model would be under that model; it would not measure the probability that the null hypothesis is true, the probability that a result occurred by chance, or the clinical importance of an effect. No primary p-value or confidence interval is reported in the registry record. It is therefore not possible to assess statistical significance or precision from the hematocrit outcome.

The record states that the primary outcome has several categories or time points and was not reduced to one comparison. That matters because an interpretation needs to identify which comparison is primary and how the multiple observations are handled. General methods can address repeated measurements and multiple comparisons in different ways, but no such method should be attributed to this trial without a report of the analysis. The registry lists 10 outcome measures and 1 analysis; this does not, by itself, specify the number of tests performed or the method used for any endpoint.

Dispersion and distribution also matter for continuous outcomes. As a general matter, a standard deviation can help readers understand the variability in observed measurements. If data are strongly skewed or contain influential values, a mean and standard deviation may not fully describe their distribution. The registry does not provide the outcome data, distributional checks, or any alternative summaries. Consequently, it is not possible to assess whether the selected summaries adequately characterize the observed hematocrit values.

For event outcomes such as infection or transfusion, analysis generally depends on the exact event definition, the period at risk and how repeated events are handled. If counts show greater variability than a simple model expects, over-dispersion can make standard errors too small unless the analysis accounts for it. This is a general consideration, not a claim about the trial’s data: the registry does not report event-level data, analysis models or checks for over-dispersion. Nor does it report enough detail to determine whether the listed adverse-event counts refer to participants with at least one event or to event totals beyond the labels accompanying those counts.

10. Multiplicity, Missing Data and Analysis Populations

The primary hematocrit measure is listed at Day 7, Day 14, Day 21 and Day 28, and the registry lists 10 outcome measures. Looking at multiple outcomes or time points can raise multiplicity concerns: as a general principle, a larger set of statistical tests can increase the chance of at least one apparently notable result even when there is no underlying difference. The record does not report a multiplicity plan, a hierarchy of outcomes, an adjustment method, or which result was designated as the principal comparison. It also does not identify an analysis that combines the listed hematocrit time points. No particular approach can be assumed.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how many participants contributed hematocrit measurements at each time point, how missing measurements were handled, or whether the primary analysis included all randomized participants, only those who received treatment, or another defined population. It also does not describe imputation, sensitivity analyses or the handling of withdrawals. These details are important because incomplete follow-up can affect both the estimated group contrast and its uncertainty, especially if missingness is related to participants’ health or assigned group.

The registry’s enrollment figure does not establish how many participants had usable primary-outcome data. The at-risk counts in the adverse-event entries are not a substitute for outcome-specific analysis denominators. Without participant flow, reasons for missing measurements and an analysis-population definition, readers cannot assess attrition or whether the analyzed groups remained comparable. The registry records 1 analysis, but that entry does not specify the analysis population, the missing-data method or whether additional analyses were conducted. These omissions limit reproducibility and make the reported design difficult to connect to a primary-outcome estimate.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event entries list 0 serious events among 97 at risk in the iron group and 0 among 103 at risk in the placebo group. For other adverse events, the record lists 7 affected among 97 at risk in the iron group and 4 among 103 at risk in the placebo group. These are recorded counts and denominators; they should not be read as a complete account of all safety outcomes or as proof of a comparative safety difference.

The registry does not report the specific terms represented by the other-event counts, event severity beyond the serious-event category, timing, duration, or whether participants experienced more than one event. It also does not provide comparative estimates or uncertainty intervals for these counts. The serious-event entries contain zero affected, but zero recorded events does not establish that the risk is absent; interpretation depends on ascertainment, follow-up and completeness of reporting.

The deaths fields are null. A null entry is not a numerical count and should not be interpreted as zero deaths. Although hospital mortality is listed as a secondary outcome, its results are not reported in the registry record. These adverse-event data therefore offer only a limited description and do not answer the trial’s full safety or mortality questions.

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

The registry record documents a randomized, placebo-controlled study of enteral ferrous sulfate in anemic, critically ill patients, with hematocrit as the primary outcome and several clinical outcomes listed as secondary measures. Its aims include investigating anemia, transfusion, mortality and infection. That design and set of aims establish what the study sought to examine, not what the results demonstrated.

The primary hematocrit results are not reported in the record. Without group summaries and an estimated comparison, it is not possible to describe the observed direction or magnitude of a difference, or its precision. The same limitation applies to the listed secondary outcomes: their names alone do not indicate whether there were differences between groups. Completion status and enrollment do not substitute for outcome findings.

The adverse-event entries provide some descriptive counts, including the serious and other event categories, but not enough detail to support a comprehensive safety comparison. In particular, the deaths fields are null, and the hospital-mortality outcome does not have a reported result in the available record. Missing information should not be converted into a claim of no events or no difference.

As a general statistical principle, a study result is interpreted using the estimated effect, its uncertainty, the analysis population and the outcome definition. Statistical uncertainty and clinical importance are related but distinct: a precise small difference and an imprecise estimate can call for different interpretations, even if a test result were similar. Because the relevant estimates are absent, neither statistical nor clinical importance can be judged from this registry record.

The most defensible conclusion is about reporting: the registry identifies the trial’s question, design and planned outcome measures, but does not provide the primary hematocrit findings needed to evaluate the principal comparison. This does not establish that the intervention had no effect, nor does it establish that it did. It leaves the central outcome question unresolved by the information recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is measured repeatedly over several specified days, while the registry record does not identify a single comparison or provide results for any of those time points. For clinical researchers, that highlights the importance of distinguishing an outcome’s measurement schedule from the analysis plan. A list of time points alone does not say whether each is tested separately, whether change over time is modeled, or how a principal result is chosen.

The design also illustrates why a randomized label cannot carry the entire interpretation. Random assignment supports a comparative framework, but readers still need the outcome definition, analysis population, missing-data approach, model and estimated uncertainty. Masking and a placebo comparator are relevant design features, yet the registry’s brief labels do not describe the operational details needed to assess their implementation.

Multiplicity is another practical issue. The record lists a primary outcome with several time points and 10 outcome measures. General statistical methods can control or structure multiple comparisons, but the registry does not report a strategy for doing so. Without such detail, a reader cannot determine how a particular result would relate to the full set of planned outcomes or whether a selective emphasis was prespecified.

Finally, the record illustrates the difference between a trial being marked completed and having interpretable results available in the registry. Enrollment, a named endpoint and a list of secondary outcomes do not reveal an effect estimate. For evidence synthesis and clinical research practice, transparent reporting of participant flow, endpoint data, estimates, uncertainty and analysis decisions is essential. In this case, the registry provides a framework for understanding the question but not the results required to answer it.

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 primary outcome entry is sparse: it names hematocrit, its unit, the summary measure and the time points, but its description and population fields are empty. The registry record does not report the observed means or standard deviations, a contrast between groups, confidence intervals or a test result. The primary outcome has several time points and is not reduced to one comparison. This prevents assessment of both the result and the method used to reach it.

Several details needed to evaluate the trial’s conduct and analysis are not reported in the registry record. These include eligibility criteria beyond the broad condition, participant characteristics, group allocation counts for the main outcomes, sequence generation, allocation concealment, masking roles, adherence, withdrawals, protocol deviations and participant flow. The record also does not state the primary analysis population or how missing measurements were addressed. These are specific gaps in the available record, not evidence that the procedures were absent.

The listed secondary outcomes are not accompanied by result estimates or detailed definitions. For example, the record does not specify how infections were classified, how repeated events were treated, or how average antibiotic use and length of stay were analyzed. The adverse-event entries provide counts, but not event terms or uncertainty estimates; the deaths fields are null. These limitations restrict interpretation of both benefits and harms recorded in the registry.

The registry lists a planning-illustration framework but does not report the trial’s own sample-size justification or numerical calculation outputs in the material available for interpretation. The record also does not describe interim analyses, a statistical analysis plan, or a multiplicity strategy. No conclusion about whether such plans existed should be drawn from their absence in this record. Overall, the registry identifies the study’s broad design and questions but lacks the result and methodological detail needed for a complete statistical appraisal.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of Enteral Iron Supplementation in Critical Illness — NCT00450177.
• Registry record last updated 2019-07-18; status last verified 2019-07.
• Results first posted 2019-07-08.
• 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 NCT00450177, titled “Efficacy of Enteral Iron Supplementation in Critical Illness.” It is listed as a completed Phase 2 randomized, parallel-group, placebo-controlled trial with quadruple masking and enrollment of 200. The sponsor is Weill Medical College of Cornell University. The recorded start is 2006-01 and primary completion is 2007-12.

The intervention was ferrous sulfate 325 mg, administered three times a day, compared with placebo on the same schedule; treatment continued until discharge or for 42 days, whichever occurred first. The primary outcome was mean hematocrit, expressed as percentage of RBC in blood, at Day 7, Day 14, Day 21 and Day 28. Listed secondary outcomes include transfusion, infection, constipation, antibiotic use, hospital mortality and length of stay.

The primary outcome results and results for the listed secondary outcomes are not reported in the registry record. Adverse-event entries include serious and other event counts, while the deaths fields are null. The record therefore describes the study’s question and design but does not permit evaluation of the principal hematocrit comparison.