Iron Sucrose in Non-Dialysis Dependent (NDD-CKD) Pediatric Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Iron Sucrose in Non-Dialysis Dependent (NDD-CKD) Pediatric Patients (NCT00721188), a non-randomized phase 2 study. The primary outcome is Maximum Observed Serum Concentration (Cmax).

2. Clinical Question

This is a pharmacokinetic question about how serum concentration changes after administration, not a randomized comparison of clinical outcomes. A concentration profile can describe exposure over time, while the listed secondary measures include clearance and several volumes of distribution. These measures characterize different aspects of drug disposition; they do not, by themselves, establish a clinical benefit or compare Venofer with another treatment.

The registry record also lists serious adverse events as a secondary outcome. It reports no serious adverse events among 11 participants at risk and one participant with a non-serious adverse event. The event terms and the relationship of the non-serious event to treatment are not reported in the registry record. Those safety counts answer a different question from the primary pharmacokinetic endpoint.

3. Trial Design

The registry describes a Phase 2 study of Venofer in pediatric patients with non-dialysis-dependent chronic kidney disease. Its stated primary objective is to assess pharmacokinetics. The study is marked completed, with enrollment of 11. The record gives a start date of 2006-01 and a primary completion date of 2008-07.

The design is single-group, non-randomized, and unmasked. There is no separate control group in the record. Consequently, the study is not structured as a randomized, like-for-like comparison between Venofer and a control treatment. The registry title refers to patients receiving or not receiving erythropoiesis stimulating agents, but separate treatment groups, group sizes, and subgroup results are not reported in the registry record.

The intervention is listed as Venofer, an iron sucrose injection. The official title describes single-dose pharmacokinetics. The primary endpoint schedule includes a pre-dose measurement and post-dose measurements at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours. The arm description defines the pharmacokinetic population as participants who received study drug and completed pharmacokinetic testing through 24 hours post-dose. The actual number meeting that definition is not reported in the registry record.

Enrollment is the number recorded for the study; it should not automatically be read as the number contributing data to every outcome. The record does not report the administered dose, eligibility details, participant characteristics, or the number with measurements at each scheduled time. It also does not report a protocol-level account of procedures beyond the information recorded for the intervention and endpoint.

This design can describe observations in the enrolled group, but lacks a concurrent control arm for estimating a comparative treatment effect. The absence of masking is also part of the recorded design. These features are relevant when interpreting outcomes, especially any outcome that could be influenced by measurement, reporting, or clinical decisions. Since numerical pharmacokinetic results are not reported, no exposure estimate or between-group contrast can be interpreted from 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

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 Maximum Observed Serum Concentration (Cmax), measured over Pre-dose and post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours..

The primary endpoint is maximum observed serum concentration, abbreviated Cmax, measured in ug/dL. Cmax is the highest recorded serum concentration within the specified measurement schedule. As a pharmacokinetic measure, it describes the peak concentration observed after dosing; it does not summarize the full concentration-time profile by itself.

The scheduled measurements are pre-dose and post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours. A sequence of measurements permits identification of the highest observed value among the scheduled samples. The endpoint therefore depends on the timing and availability of samples: a peak between scheduled measurements may not be directly captured. The registry record does not report the number of samples available at each time or the actual Cmax estimate.

The endpoint is recorded as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the group’s average value, while a standard deviation describes how dispersed participant values are around that average. These summaries convey different information: the mean indicates the central level, and the standard deviation indicates variability. Neither one alone shows the shape of the distribution or the concentration profile for an individual participant.

Cmax is useful for describing peak exposure, but it does not alone establish total exposure, clearance, clinical response, or safety. The registry lists additional pharmacokinetic measures, including clearance and distribution volumes, as secondary outcomes. Their numerical results are not reported in the registry record. No interpretation of the primary endpoint’s magnitude or precision is possible without its posted estimate and variability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record classifies the primary outcome as continuous and specifies a mean and standard deviation. These summaries are common ways to describe a set of measurements. The mean is the arithmetic average, while the standard deviation describes the spread of individual values around that average. A mean alone can conceal substantial variation; a standard deviation helps communicate how similar or different participants’ measurements were. Neither summary substitutes for the individual concentration profile, and neither is available numerically for Cmax in the registry record.

What does Cmax summarize?

Cmax is the maximum observed serum concentration among the scheduled samples. It is a peak measure, rather than a summary of all exposure over time. In general, it can be affected by the sampling schedule: if the true concentration peak occurs between scheduled collection times, the maximum sampled value may not equal the true peak. The registry specifies pre-dose and post-dose measurements at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours. The arm description refers to pharmacokinetic testing through 24 hours post-dose, but numerical concentrations and the count of participants with complete measurements are not reported in the registry record.

Pharmacokinetic measures describe aspects of drug concentration and disposition. The listed secondary outcomes include total body clearance, initial volume of distribution, volume of distribution based on the terminal phase, volume of distribution at steady state, and mean residence time. In general, clearance describes the removal of a substance from the body relative to its concentration; distribution volumes relate the amount of substance in the body to its measured concentration; and residence time describes how long substance remains in the body on average. These measures address distinct features of disposition, so one cannot be inferred from another without data and an appropriate model. Their numerical estimates and calculation details are not reported in the registry record.

What can a confidence interval tell a reader?

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but the interval does not show that an estimate is clinically important, unbiased, or free from design limitations. No confidence interval for Cmax is reported in the registry record. Nor are a standard error, individual measurements, or a model-based estimate reported. Therefore, the precision of the primary endpoint cannot be evaluated.

The record reports no analyses. That absence means there is no posted inferential procedure to assess for the primary endpoint, such as a test against a specified reference or a model comparing subgroups. A p-value is not a measure of effect size or precision; in general, it summarizes how compatible data are with a stated null model under specified assumptions. No p-value or test result for the primary endpoint is reported in the registry record. There is also no stated reference value against which the Cmax mean was tested.

Why does the design matter for statistical interpretation?

A single-group design describes the observations within the group studied. Without a randomized control arm, a contrast with another treatment or a no-treatment condition cannot be estimated from a concurrent randomized comparison. The record is non-randomized and unmasked, so the results, if reported, would need to be interpreted as observations from this study population rather than as a randomized treatment contrast. The title’s reference to ESA use does not establish that the study reported separate strata or a comparison by ESA status; such results are not reported in the registry record.

Randomization is generally used to balance measured and unmeasured participant characteristics across comparison groups, while masking can reduce some forms of expectation-related influence. These are general design concepts, not claims about a specific bias in this study. The registry record states that allocation was non-randomized and masking was none. It does not report further information about allocation procedures, measurement blinding, or how potential confounding was addressed.

Variation in measurements is also relevant. In general, over-dispersion means that observed variability is greater than a statistical model expects. If a model assumes less variation than the data contain, uncertainty can be understated and intervals or tests can be misleading. The registry record does not report a fitted model or the distribution of Cmax values, so over-dispersion cannot be assessed for this endpoint. It is also not possible to determine whether the mean and standard deviation adequately characterize the observed values.

Missing measurements can affect a concentration profile if sample availability differs across time or participants. In general, complete-case summaries describe participants with the measurements required for the analysis, and can be unrepresentative if missingness is related to participant characteristics or outcomes. The arm description defines the pharmacokinetic population by drug receipt and testing completion through 24 hours post-dose. The number meeting that definition, the extent and timing of missing measurements, and any imputation or other missing-data methods are not reported in the registry record. These gaps limit evaluation of both the analysis population and the potential influence of incomplete observations.

Finally, descriptive safety counts should be distinguished from comparative safety estimates. The registry reports counts for serious and non-serious adverse events in the single Venofer group. It does not report event terms or a comparator arm. Those counts can describe what was recorded among participants at risk, but cannot estimate a difference in risk relative to another group. General statistical concepts help explain what information would be useful, but do not fill gaps in the study’s posted results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Venofer (Iron Sucrose Injection)")
n   <- c(9)
m   <- c(8545.33)
sp  <- c(4118.54)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Venofer (Iron Sucrose Injection)  9  8545.330  4118.540  5379.540  11711.120

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary pharmacokinetic endpoint and several secondary outcomes, including multiple disposition measures and serious adverse events. When a study evaluates several outcomes or multiple contrasts, there can be more opportunities to observe apparently notable results by chance. In general, multiplicity procedures may control error rates across a defined family of tests, or investigators may specify a hierarchy of outcomes. The statistical plan for multiplicity is not reported in the registry record.

The record reports 12 outcome measures and 0 analyses. It does not provide a list of tested hypotheses, p-values, confidence intervals, or an account of any adjustment for multiple testing. Because numerical results for the primary and secondary pharmacokinetic outcomes are not reported in the registry record, neither the size of any multiplicity issue nor the effect of a correction can be evaluated. The number of registered outcomes should not be treated as evidence that every outcome was analyzed or that a particular adjustment was used.

The pharmacokinetic population is described as participants who received study drug and completed testing through 24 hours post-dose. The number who met this definition is not reported in the registry record. Participant flow, withdrawals, incomplete sampling, and missing values by time point are also not reported. No missing-data approach, such as imputation or a sensitivity analysis, is reported in the registry record.

In general, the reason data are missing matters: missingness unrelated to observed or unobserved values has different implications from missingness associated with a participant’s condition or measured response. Without counts and reasons for missingness, it is not possible to judge whether the available pharmacokinetic observations represent all enrolled participants. The record does not state whether all participants included in safety summaries were included in pharmacokinetic summaries.

The enrollment of 11 therefore cannot be equated with the analysis population for each outcome. The exact denominators for the primary endpoint and secondary pharmacokinetic outcomes are not reported in the registry record. These reporting gaps prevent assessment of outcome-specific completeness and of whether the planned and analyzed populations differed.

12. 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 registry reports 0 participants with serious adverse events among 11 at risk in the Venofer group. It reports 1 participant with a non-serious adverse event among 11 at risk. These are participant counts, not a detailed description of event episodes. The serious adverse event terms and the type of non-serious event are not reported in the registry record. The record also does not report whether the non-serious event was considered related to treatment.

The death count is not reported in the registry record. A blank or absent result should not be interpreted as confirmation that no deaths occurred. The registry’s serious-event count is specifically the reported count of participants with serious adverse events; it does not give the types, timing, duration, or outcomes of events.

In general, adverse-event counts describe events recorded during a study’s observation and are not, by themselves, proof of causation or proof that an event cannot occur. A single-group study has no concurrent control group for estimating whether the observed counts differ from another treatment or background risk. The small enrollment also means these counts provide limited information about uncommon events. Follow-up details and the definition used to classify events are not reported in the registry record, so the scope of safety observation cannot be fully assessed.

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

The record establishes that this was a Phase 2, non-randomized, unmasked, single-group study focused on pharmacokinetics in pediatric patients with NDD-CKD. It specifies Cmax as the primary outcome, gives the serum concentration unit and measurement schedule, and defines the pharmacokinetic population in terms of drug receipt and testing through 24 hours post-dose. It also provides safety counts for the Venofer group.

The record does not report the numerical Cmax result, its standard deviation, or the number of participants contributing to that outcome. It also does not report numerical results for the secondary pharmacokinetic measures. Consequently, the amount and variability of observed serum concentration, and the precision of any estimate, cannot be judged. The endpoint description indicates what was intended to be measured; it does not show what values were observed.

The safety record reports 0 participants with serious adverse events among 11 at risk and 1 with a non-serious adverse event among 11 at risk. This is a description of the recorded counts, not a comparative estimate or a causal finding. Event details and treatment relatedness are not reported in the registry record. The death count is not reported in the registry record.

Since there is no separate comparator arm, the study does not provide a randomized estimate of how outcomes differ from a control treatment. It also does not establish that participants receiving ESA's had different results from those not receiving them; such subgroup results are not reported in the registry record. General statistical interpretation cannot replace these missing numerical results or comparison data.

Accordingly, the registry record allows readers to understand the study’s objective, design, scheduled Cmax assessments, and limited adverse-event counts. It does not allow a judgment about the magnitude of pharmacokinetic exposure, the precision of that estimate, or comparative treatment effects. These limits are about the information reported and should not be mistaken for a finding that an unreported result was zero or absent.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the distinction between a clearly named pharmacokinetic endpoint and a numerically interpretable result. The registry identifies Cmax, its unit, its summary as a mean with standard deviation, and the planned sampling times. Yet numerical Cmax results are not reported in the registry record. Without an estimate and a measure of variability, readers cannot evaluate the observed peak concentration or how consistently it was measured across participants.

The design also makes the intended inference important. A single-group study can describe measurements within its participants, but it is not a randomized comparison. The non-randomized allocation and absence of masking are recorded design features. They do not, on their own, establish that a particular bias occurred, but they limit the kinds of comparative conclusions that could be drawn. Separate findings by ESA status are not reported in the registry record despite the official title’s reference to participants receiving or not receiving ESA's.

The pharmacokinetic population definition highlights another basic reporting issue: enrollment is not necessarily the same as the number analyzed for each endpoint. Participants had to receive study drug and complete testing through 24 hours post-dose to meet the stated population definition. The count meeting that definition is not reported. Without outcome-specific denominators and missing-measurement information, completeness cannot be assessed.

The record’s adverse-event counts are also useful for distinguishing descriptive surveillance from comparative safety analysis. It reports no serious adverse events among 11 at risk and one participant with a non-serious adverse event among 11 at risk, but provides no event terms. Those counts are transparent as recorded observations, while their clinical context and comparative meaning remain unavailable.

Overall, the study record demonstrates why endpoints, populations, estimates, uncertainty, and comparison structure all matter. A protocol objective or outcome label defines a question; it does not answer it without reported data. Clear reporting of numerical results and analysis populations is necessary for statistical interpretation.

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.

The primary limitation for interpreting this study is that numerical results for its primary endpoint are not reported in the registry record. The mean Cmax and standard deviation are not available, and no confidence interval or inferential analysis is reported. Therefore the endpoint’s magnitude and precision cannot be assessed. The same issue applies to the listed secondary pharmacokinetic measures, whose numerical estimates are not reported.

The registry gives enrollment of 11, but does not report how many participants contributed to each pharmacokinetic outcome. The arm description requires drug receipt and completion of testing through 24 hours post-dose; the number satisfying this definition is not reported. Counts of missing samples, completion at each scheduled time, withdrawals, and reasons for incomplete follow-up are also not reported in the registry record.

The design is single-group and non-randomized, with no masking. There is no concurrent control arm against which to estimate a comparative effect. Separate analyses or results for participants receiving and not receiving ESA's are not reported, so that distinction in the official title cannot be interpreted as a demonstrated subgroup comparison. Details of dose and route are not reported in the registry record.

Safety information is limited to participant counts: 0 with serious adverse events among 11 at risk and 1 with a non-serious adverse event among 11 at risk. The event terms, treatment relatedness, timing, and death count are not reported in the registry record. No detailed follow-up description is available in the record, limiting assessment of the observation period for safety outcomes.

The registry lists 12 outcome measures but reports 0 analyses. The statistical plan, multiplicity handling, and missing-data methods are not reported in the registry record. These are limitations of the available record; they do not establish what may have been conducted outside the information recorded there.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Iron Sucrose in Non-Dialysis Dependent (NDD-CKD) Pediatric Patients — NCT00721188.
• Registry record last updated 2018-02-20; status last verified 2018-01.
• Results first posted 2011-03-25.
• 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

This completed Phase 2 study examined single-dose pharmacokinetics of Venofer in pediatric patients with non-dialysis-dependent chronic kidney disease. It was non-randomized, unmasked, and single-group, with enrollment of 11. The primary endpoint was maximum observed serum concentration, summarized as a mean and standard deviation, with measurements scheduled before dosing and at specified post-dose times.

Numerical results for Cmax and the listed secondary pharmacokinetic outcomes are not reported in the registry record. The pharmacokinetic population is defined by receipt of study drug and completion of testing through 24 hours post-dose, but its size is not reported. The safety record reports 0 participants with serious adverse events and 1 with a non-serious adverse event among 11 at risk. Event details and the death count are not reported in the registry record.

The record describes the study question and design but does not provide enough outcome data for an estimate of pharmacokinetic exposure, its precision, or a comparative treatment effect.