A Clinical Study of Xenetix 300 in Multislice Computed Tomography (CT) Pediatric Indications: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Study of Xenetix 300 in Multislice Computed Tomography (CT) Pediatric Indications (NCT00347022), a randomized phase 4 study. The primary outcome is Creatinine Clearance.

2. Clinical Question

The posted comparison gives a mean difference of 0.8 percentage points in the direction Visipaque minus Xenetix, with a confidence interval from -6.426 to 8.026 and an unadjusted p-value of 0.828. Those figures describe the observed outcome and its uncertainty in the posted analysis; interpretation also depends on the outcome population, analysis choices, and clinical context, which are not fully detailed in the registry record.

3. Trial Design

The registry record describes a phase 4, randomized, triple-masked, parallel-group study sponsored by Guerbet. Its listed condition is Diagnostic Imaging, and the brief description identifies pediatric multislice computed tomography indications. The record lists Xenetix and Visipaque as drug interventions. Participants in the Xenetix arm received one injection of Xenetix 300 (300 mg of iodine/ml); participants in the Visipaque arm received one injection of Visipaque 270 (270 mg of iodine/ml).

The study start is recorded as 2006-05, primary completion as 2009-04, and status as COMPLETED. The registry record lists enrollment of 145. The primary outcome data, however, report 62 participants for Xenetix and 66 for Visipaque. The adverse-event groups list 74 at risk for Xenetix and 71 at risk for Visipaque. The registry record does not explain the differences among these counts, whether they reflect different analysis populations, or how participants without posted primary outcome values were handled.

Randomization indicates that allocation was intended to be assigned by chance, while triple masking indicates that the record classifies the study as masked at three levels. The identities of those masked, the method of sequence generation, allocation concealment, and details about how masking was maintained are not reported in the registry record. A parallel model means the interventions are organized as separate study arms rather than as a within-participant crossover comparison. The registry record does not provide the original protocol or detailed operational methods, so further design specifics should not be inferred from these labels.

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: Any patient having a creatinine clearance \< 60ml/min/1.73m² at time of baseline blood sample and/or positive beta HCG (Human Chorionic Gonadotropin) within 48h before contrast medium administration was considered as immediate withdrawal from trial

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 Creatinine Clearance, measured over between 48h before the contrast medium administration and 72h +/-12h after contrast medium administration.

The primary endpoint is mean percent change in creatinine clearance, measured between 48h before contrast medium administration and 72h +/-12h after administration. Creatinine clearance is a measure related to kidney filtration. A before-and-after change can describe how the measure differs over the specified period surrounding contrast administration, while a comparison between randomized arms can estimate how the reported average changes differed between the two intervention groups.

The endpoint is continuous: each participant's measurement can take a range of values, and the posted arm results are expressed as means with standard deviations. The record describes the outcome as the variation in creatinine clearance before and after product injection. It does not provide a fuller measurement protocol, including how clearance was determined, the exact calculation of percent change, or how measurements outside the stated time window were handled. The endpoint population is also not specified.

This outcome is useful for statistical comparison because the arm means and their variability can be summarized, and an estimated mean difference can be accompanied by a confidence interval. Such an endpoint does not automatically establish a clinically meaningful difference: that requires a clinical interpretation or threshold, neither of which is reported in the registry record. The outcome should therefore be read as a measure of observed change over the stated period, not as a complete assessment of longer-term kidney function or of all consequences of either intervention.

7. Results Posted in the Registry

• Visipaque: mean 1.90 versus 1.10 on control; difference 0.80 (95% CI -6.43 to 8.03), standardized effect d = 0.04; z-test p = 0.828.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement, and the posted arm summaries use a mean and standard deviation. The comparison is expressed as a mean difference between Visipaque and Xenetix. The posted arm means are 1.9 for Visipaque and 1.1 for Xenetix; the comparison estimate is 0.8, in the stated direction Visipaque minus Xenetix. A mean difference keeps the outcome in its original unit, here percent change, and provides a direct estimate of the separation between group averages.

What does the standard deviation describe?

A standard deviation describes the spread of individual observations around their group mean. It is not the uncertainty of the mean itself and is not a confidence interval. The reported standard deviations are 19.7 for Xenetix and 22.0 for Visipaque. Their size relative to the means signals that individual changes varied considerably. General statistical context: greater variability makes it harder to estimate a group mean difference precisely when the sample sizes are held fixed. It also means that a mean difference is a summary of group averages, not a prediction that every participant's outcome is near that average.

What does the confidence interval add?

The comparison confidence interval runs from -6.426 to 8.026. It communicates uncertainty around the estimated mean difference, in the same direction and scale as the estimate. Under the statistical model used to construct it, the interval describes a range of values reasonably compatible with the observed data. It is not a range containing a specified fraction of individual participant outcomes, nor does it mean there is a particular probability that the true value lies inside this one calculated interval. The registry record does not identify all details of the interval calculation or state whether it was adjusted for any other analyses.

How should the p-value be read?

The posted unadjusted p-value is 0.828. A p-value is calculated under a null hypothesis and statistical model; it quantifies how unusual a result at least as inconsistent with that null would be if the model and null hypothesis applied. It is not the probability that the null is true, and it does not measure the size or clinical importance of the difference. The label unadjusted indicates that the value is not presented as adjusted for multiplicity. Whether adjustment was planned or appropriate is not reported in the registry record.

General statistical context: statistical significance and clinical importance are different questions. A result can be statistically inconclusive while the confidence interval still permits effects that matter clinically, or it can be statistically distinguishable from zero yet small in clinical terms. Judging importance requires an appropriate clinical threshold and adequate knowledge of the measurement and population. Neither a clinical threshold nor a full endpoint measurement protocol is reported in the registry record.

Why does variability matter?

For continuous outcomes, analysis commonly compares means while accounting for how variable the observations are and how many contribute to each group. Here, the outcome summaries report 62 Xenetix participants and 66 Visipaque participants. The registry record does not describe the exact primary analysis procedure, assumptions checked, handling of missing observations, or any covariate adjustment. The posted mean difference and interval can therefore be described, but the underlying analysis choices cannot be reconstructed in full from the registry record.

General statistical context: if outcome variability is greater than anticipated, confidence intervals tend to be wider and a study may have less ability to distinguish a real difference from random variation. In settings where data are more dispersed than a simple model assumes, methods that address over-dispersion or use robust uncertainty estimates may be considered. There is no report in the registry record that over-dispersion was assessed or that such methods were used; moreover, the endpoint is continuous rather than a posted event-count outcome.

The comparison is described alongside the arm summaries, but the registry record lists no posted analyses. The recalculated comparison should be read as an unadjusted comparison based on the posted summary statistics, not as a substitute for details of a prespecified sponsor analysis. The record indicates no discrepancy, and no sponsor analysis details are available for further comparison. A confidence interval and p-value do not resolve questions about participant exclusions, missing data, protocol deviations, or outcome ascertainment; those require reporting of the analysis population and methods.

10. Confidence Intervals and Precision

The estimated mean difference in percent change is 0.8 for Visipaque minus Xenetix. Its confidence interval extends from -6.426 to 8.026. The interval is centered around an estimate close to zero, but it spans values below and above zero. As a result, the posted comparison leaves uncertainty about both the direction and magnitude of the underlying mean difference.

A confidence interval is a measure of statistical precision, not a statement about the spread of individual participant outcomes. The standard deviations of 19.7 for Xenetix and 22.0 for Visipaque describe participant-level variability; the confidence interval instead describes uncertainty around the group contrast under the analysis assumptions. General statistical context: narrower confidence intervals indicate greater precision, whereas wider intervals leave more plausible values compatible with the observed data.

The lower and upper ends of the interval should not be treated as clinical boundaries. The registry record does not report a clinically important difference, an equivalence margin, or a non-inferiority margin. It therefore cannot establish whether all values in the interval would be clinically negligible, or whether some would matter. The unadjusted p-value of 0.828 is consistent with the interval crossing zero, but neither statistic establishes equivalence.

Precision also depends on the information included in the analysis. The primary outcome counts are 62 and 66, while enrollment is listed as 145. The record does not explain this distinction, describe missing outcome data, or identify the primary analysis population. These omissions limit the ability to evaluate the source of uncertainty and the extent to which the estimate represents all enrolled participants.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations translate the observed mean difference into planning examples for future studies. Because the primary endpoint is continuous, the figures are participants per arm, not total event counts. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect set at the stated fraction of the observed effect. These are planning assumptions for the illustration; the registry record does not report the original trial's sample-size assumptions or justification.

For planning at 100% of the observed effect, the illustration gives 10,733 participants per arm for 80% power and 14,368 participants per arm for 90% power. For planning at 75% of the observed effect, it gives 19,081 participants per arm for 80% power and 25,543 participants per arm for 90% power. For planning at 50% of the observed effect, it gives 42,931 participants per arm for 80% power and 57,472 participants per arm for 90% power.

In plain terms, 80% power is the planned probability of detecting an effect of the specified size under the illustration's assumptions, if that effect is present. The 90% power column describes a higher target probability under those same assumptions. A smaller effect is harder to distinguish from random variation, so it requires more participants to reach either target. The curve represents the same general relationship between assumed effect size and planning sample size; its values depend on the stated assumptions. These figures are not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.800; pooled standard deviation σ = 20.918.
2. n = 2 × (1.96 + 0.842)² × 20.918² / 0.800² = 10,732.5, rounded up to 10,733 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.8                      # observed difference in means
sigma <- 20.9181113141789                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(347022)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 10,733 (80% power), 14,368 (90% power)
 75% of observed effect: n per arm = 19,081 (80% power), 25,543 (90% power)
 50% of observed effect: n per arm = 42,931 (80% power), 57,472 (90% power)
power.t.test: 10733.5 
Simulated power at n = 10,733 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no secondary outcomes. It lists no analyses, and does not report an interim analysis plan, a multiplicity strategy, or an analysis hierarchy. The primary comparison's p-value is identified as unadjusted. Without a complete analysis plan, it is not possible to determine whether other comparisons or outcome assessments were conducted, whether testing was restricted to a single prespecified primary contrast, or whether any adjustment was intended.

Multiplicity refers generally to the increased chance of a false-positive finding when many statistical tests are performed. General statistical context: decisions about multiplicity depend on the set of planned tests and the goals of the analysis. No assumptions about those choices should be made from the single posted outcome result. The record also does not identify whether any interim review of accumulating outcomes took place.

The primary outcome population is not reported in the registry record. The primary endpoint counts are 62 in the Xenetix group and 66 in the Visipaque group, whereas the record lists enrollment of 145. The adverse-event groups separately list 74 and 71 at risk. The record does not say whether these counts correspond to intention-to-treat, per-protocol, evaluable, or other analysis populations, and does not reconcile them.

Missing-data methods are also not reported in the registry record. There is no description of how unavailable measurements were handled, whether reasons for missingness were recorded, or whether sensitivity analyses were performed. These details matter because the interpretation of a group comparison can depend on who contributed outcome data and why other observations were absent. No conclusions about bias from missing data or the population represented by the analysis can be drawn from the counts alone.

14. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: surgery of vesical wound (1.4%), meningitis (1.4%), ent surgery (1.4%), mastoidectomy (1.4%), myelofibrosis (1.4%).

The registry record lists serious adverse events for 5 of 74 participants at risk in the Xenetix safety group and 4 of 71 at risk in the Visipaque safety group. For other adverse events, it lists 11 of 74 at risk for Xenetix and 13 of 71 at risk for Visipaque. These are posted counts and denominators; no comparative safety analysis or confidence intervals are reported. The registry record does not specify the definitions, collection window, attribution rules, or analysis population for these safety summaries.

The adverse-event group label is recorded as Vispaque, whereas the intervention and outcome arm are named Visipaque. The listed serious-event terms are Surgery of vesical wound, Meningitis, Ent surgery, Mastoidectomy, Myelofibrosis, and Operation of the mediastinal haematoma, each reported as 1.4%. The record does not assign those terms to a particular intervention arm in the posted listing, so they should not be attributed to one group. Death counts are not reported in the registry record; an unreported count should not be read as zero.

These figures are descriptive. Differences in raw counts cannot establish a comparative safety effect, particularly without fuller information about events, exposure, and analysis methods.

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

The posted primary result describes average change in creatinine clearance over the stated period surrounding contrast medium administration. The mean change was 1.1 in the Xenetix arm and 1.9 in the Visipaque arm. The estimated mean difference was 0.8 in the direction Visipaque minus Xenetix, with a confidence interval from -6.426 to 8.026 and an unadjusted p-value of 0.828.

This result does not establish that the interventions have identical effects. A conventional non-significant comparison does not demonstrate equivalence, and the registry record does not report an equivalence margin or a non-inferiority design. The confidence interval includes zero as well as values in either direction, so the estimate is not precise enough to settle the direction of the mean difference. The clinical significance of the range cannot be determined without a meaningful threshold, which is not reported in the registry record.

The result also does not describe every participant's response. The group standard deviations are 19.7 and 22.0, reflecting substantial variability around the arm averages. The endpoint concerns a specified measurement window, from 48h before administration to 72h +/-12h afterward; it does not provide evidence about longer-term changes. No secondary outcome results are posted, and the registry record does not provide the outcome population or details of missing data.

The safety counts are descriptive counts among those listed at risk, not proof of a causal difference between groups. The registry record does not report comparative safety estimates, exposure-adjusted analyses, or sufficient details about event ascertainment to support a broader safety conclusion. Overall, the posted evidence supports a cautious reading of the estimated short-term mean difference and its uncertainty, rather than a claim that either intervention is better, worse, or interchangeable.

16. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should focus on an estimate and its uncertainty, not only on a p-value. The primary comparison reports a mean difference of 0.8, but the confidence interval ranges from -6.426 to 8.026. That interval communicates that the data are compatible with a range of possible differences, including values in either direction. The p-value of 0.828 alone cannot show that the interventions are equivalent or that the outcome is clinically unimportant.

The endpoint is continuous and notably variable in the posted summaries: the standard deviations are 19.7 and 22.0. This makes the distinction between participant-level spread and uncertainty around the mean contrast especially important. Statistical interpretation should also consider whether the analysis population and missing-data approach are clear enough to understand which participants the estimate represents. The registry record leaves those details unresolved.

The planning illustrations show another general statistical point: detecting smaller effects calls for larger planned sample sizes under the stated assumptions. Those figures are not a reconstruction of the trial's design rationale. The original sample-size justification and assumptions are not reported in the registry record. Keeping illustrative planning calculations separate from actual trial design prevents readers from mistaking a retrospective exercise for the study's prospective plan.

Finally, the posted safety counts cannot stand in for a complete comparative safety analysis. The denominators, event definitions, and analysis methods need context, and the serious-event terms are not linked to a particular arm in the listing. Together, these features make the record useful for examining endpoint interpretation, precision, planning assumptions, and reporting gaps, while limiting stronger conclusions from the posted results.

17. 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 reporting gaps constrain interpretation. Although enrollment is listed as 145, the primary outcome summaries include 62 Xenetix participants and 66 Visipaque participants. The adverse-event groups list 74 and 71 at risk. The registry record does not explain these different counts, specify the analysis populations, or report whether every enrolled participant was assessed for the primary outcome. It is not possible to infer reasons for the difference or to determine how it affects the estimate.

The record gives the endpoint description and measurement window, but not the detailed creatinine-clearance measurement method, the exact percent-change calculation, or the handling of measurements outside the target time. The population description is brief, and age details or other eligibility characteristics are not reported in the registry record. Such details could help clarify to whom the result applies, but should not be guessed.

There are no posted secondary outcome results and no listed analyses. The statistical analysis plan, original sample-size rationale, missing-data methods, interim-analysis procedures, and multiplicity approach are not reported in the registry record. The posted comparison therefore cannot be fully checked against a prespecified analysis plan. The record also does not report a clinical importance threshold or equivalence margin, so the interval cannot be translated into a conclusion about clinical equivalence.

Safety reporting is limited to counts and a list of serious-event terms. Event definitions, attribution, timing, and comparative analyses are not reported. The safety group is labeled Vispaque while the intervention is called Visipaque; the record does not explain the naming difference. Death counts are not reported in the registry record. These limitations warrant a descriptive rather than definitive reading of both the primary outcome and the adverse-event summaries.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Clinical Study of Xenetix 300 in Multislice Computed Tomography (CT) Pediatric Indications — NCT00347022.
• Registry record last updated 2013-04-09; status last verified 2013-04.
• Results first posted 2013-04-09.
• 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.

21. Record Summary

NCT00347022 is a completed phase 4, randomized, triple-masked, parallel-group study sponsored by Guerbet. It examined Xenetix 300 and Visipaque 270 in pediatric multislice CT indications. The registry record lists enrollment of 145, a study start of 2006-05, and primary completion of 2009-04.

The primary outcome was percent change in creatinine clearance between 48h before contrast medium administration and 72h +/-12h afterward. The posted mean difference, Visipaque minus Xenetix, is 0.8, with a confidence interval from -6.426 to 8.026 and an unadjusted p-value of 0.828. The outcome counts are 62 for Xenetix and 66 for Visipaque; their relationship to enrollment is not explained in the registry record.

Serious adverse events were reported for 5 of 74 at risk in the Xenetix group and 4 of 71 at risk in the Visipaque safety group. The record does not report deaths, detailed analysis methods, missing-data handling, or the original sample-size rationale. The posted comparison is inconclusive about the direction and clinical importance of the mean difference.