A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children (NCT00468819), a non-randomized phase 1 study. The primary outcome is Plasma Clearance Estimates of Gadobutrol by Age Group.

2. Clinical Question

3. Trial Design

This was a completed phase 1, open-label, multicenter study of gadobutrol for MRI in children and adolescents. The registry describes its design as non-randomized and single-group. Enrollment was 140. The study started in 2007-05, and primary completion was recorded in 2008-04.

Participants received one intravenous bolus injection of gadobutrol at 0.1 mmol/kg body weight, also stated as 0.1 mL/kg body weight. The record identifies age-based groups of 2 to 6 years, 7 to 11 years, and 12 to 17 years, as well as a combined age 2 to 17 years group. These are age strata rather than separate randomized treatment arms. No active comparator is described.

The primary outcome concerned median plasma clearance by age group during the period from injection up to 8 hours after injection. The registry also lists outcomes involving urinary excretion, technical adequacy and contrast quality of MRI images, and lesion assessment. There are 18 outcome measures listed, while the registry records 0 analyses. The clearance results and the other outcome results are not reported in the registry record.

The study is marked completed. The registry record does not describe a sample-size justification, allocation procedures beyond the non-randomized designation, or detailed operational methods. The enrollment figure is not necessarily the number included in every endpoint analysis; analysis-specific participant counts are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Final pharmacokinetics (PK) analysis set

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 Plasma Clearance Estimates of Gadobutrol by Age Group, measured over From injection of Gadobutrol up to 8 hours after injection..

The primary endpoint was plasma clearance of gadobutrol, expressed in L/h, summarized as a median with an inter-quartile range for each age group. The measurement period ran from injection up to 8 hours after injection, and the stated analysis population was the final pharmacokinetics analysis set.

As a general pharmacokinetic concept, clearance describes the volume of plasma from which a substance is removed over a given unit of time. It is used to characterize drug disposition, rather than to measure whether an imaging examination detects disease or improves a clinical outcome. Reporting estimates by age group can describe how the pharmacokinetic measure varies across the studied age strata, but age-group estimates alone do not establish that age caused any difference.

The median gives a measure of the center of the observed distribution, while the inter-quartile range describes the spread of its middle half. These summaries can be useful when a distribution is not well represented by a mean and standard deviation. The registry record identifies this summary approach but does not report the median clearance estimates, the inter-quartile ranges, or the number of participants contributing to each estimate. Consequently, the primary endpoint’s observed magnitude and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary represent?

The primary endpoint is a median clearance estimate, with an inter-quartile range, for each age group. As a general statistical explanation, a median is the central value when observations are ordered. It is less affected than the mean by unusually high or low observations. The inter-quartile range reports the span between the lower and upper quartiles and describes the spread of the central portion of the observations. It is a measure of variability, not a confidence interval for the median.

A confidence interval, as a general statistical concept, expresses uncertainty around an estimated quantity under a statistical procedure. The registry record names an inter-quartile range as the endpoint’s dispersion measure, but does not report confidence intervals or the endpoint estimates themselves. Without the estimate and a measure of its uncertainty, readers cannot judge how precisely the study characterized plasma clearance.

Why use age groups?

Age-specific summaries can describe whether a pharmacokinetic measure differs across the age strata used in the study. Here, the listed strata are 2 to 6 years, 7 to 11 years, and 12 to 17 years, with a combined age 2 to 17 years group also recorded. As a general statistical caution, separate descriptive estimates do not by themselves test whether group differences are larger than expected from sampling variability. The registry record does not report a statistical test, model, confidence interval, or adjusted comparison for age groups.

The design is recorded as single-group and non-randomized. Thus, the age groups should not be read as if participants had been randomly assigned to different treatments. A randomized treatment comparison aims to balance participant characteristics between treatment groups through assignment; that is not the design. The registry record does not report a comparator group or a causal analysis.

How should the safety counts be read?

The adverse-event information gives the number of participants at risk and the number affected within each recorded group. These are participant counts, not necessarily counts of all event episodes. A participant may experience more than one event, and the registry record does not provide enough detail to determine event-level recurrence or the criteria used to classify events. The record lists serious adverse events separately from other adverse events. Those categories should not be combined or interpreted as equivalent measures.

As a general statistical point, a count from a modest group can be imprecise, and a zero count does not establish that the underlying event risk is zero. The registry record does not report confidence intervals for the adverse-event counts. It also does not report attribution assessments that would establish whether events were considered related to gadobutrol.

What do planning calculations mean?

Any sample-size figures associated with the posted results are planning illustrations based on an observed effect, not the trial’s own design justification and not observed power. The described assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event calculations, the reported quantity is the total number of events; other calculations are expressed as participants per arm for 80% power or another stated power level.

As a general statistical explanation, a planning calculation asks how much information a hypothetical future design might require under specified assumptions. It does not show the probability that the completed study “had power” after its results are known. The record describes this trial as single-group and non-randomized, so a two-arm planning illustration should not be mistaken for the design used in the trial. The actual trial’s sample-size justification is not reported in the registry record.

What analysis details are absent?

The registry identifies the final pharmacokinetics analysis set as the primary endpoint population, but does not report how that set was defined, the number included, or how missing measurements were handled. It lists 18 outcome measures and 0 analyses. No model specifications, statistical test results, adjustment strategy, or endpoint estimates are reported in the registry record. These omissions limit independent assessment of both the analysis and its precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including the primary plasma-clearance endpoint and secondary outcomes covering urinary excretion, MRI image adequacy and contrast quality, and lesion assessments. The record lists 0 analyses. It does not report a multiplicity strategy, such as a hierarchy of outcomes or adjustment for repeated statistical testing. Without such information and without reported test results, the probability of false-positive findings across multiple analyses cannot be evaluated.

The primary endpoint population is named as the final pharmacokinetics analysis set. The registry record does not report its eligibility rules, its size, or how participants with missing measurements were treated. It also does not state whether measurements were imputed, excluded, or handled through another method. The number of participants contributing to each age-specific estimate is not reported in the registry record.

The overall enrollment is 140, while the combined safety group lists 138 participants at risk. The record does not explain the difference. It is not possible to determine from the registry record whether this reflects eligibility for a particular analysis, unavailable data, or another reason.

These gaps matter because the analysis population and missing-data handling affect which observations contribute to an estimate and how representative that estimate may be. The record does not report sensitivity analyses addressing missing data, nor does it report a statistical analysis plan that would clarify which outcomes and comparisons were prespecified.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.3%), crystal urine (2.3%), meningitis (2.2%).

The registry reports serious adverse-event counts by age group. In the 2 to 6 years group, 1 participant was affected among 46 at risk; in the 7 to 11 years group, 1 among 44; and in the 12 to 17 years group, 0 among 48. The combined age 2 to 17 years group lists 2 affected participants among 138 at risk. The other-adverse-event counts are 17 among 46, 16 among 44, and 16 among 48 for the age-specific groups, and 49 among 138 in the combined group.

The registry also lists Pneumonia and Crystal urine at 2.3% each, and Meningitis at 2.2%, among its top serious terms. The record does not report further detail about the definitions, attribution, timing, or participant-level overlap for these terms. Death counts are not reported in the registry record.

These counts describe events recorded during the study; they do not establish that gadobutrol caused an event. They also should not be interpreted as a comparison with another treatment, because no randomized comparator group is reported. The registry record does not provide confidence intervals for these counts.

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

The registry record establishes that a phase 1 study examined gadobutrol pharmacokinetics in children and adolescents, with plasma clearance as the primary endpoint. It specifies the dose, the single-bolus administration, the age groups, the measurement window, and the summary measure. It also reports participant counts for serious and other adverse events. These details describe what the study set out to assess and provide limited safety-count information.

The record does not report the median clearance estimates or inter-quartile ranges. It therefore does not show the observed clearance values or their variability by age group. It also does not report endpoint confidence intervals, statistical tests, or detailed analysis methods. The registry record cannot support a conclusion about the size or precision of any age-related difference in clearance.

Although MRI image-quality and lesion-related outcomes are listed, their results are not reported in the registry record. The primary endpoint itself concerns pharmacokinetics, not diagnostic accuracy, clinical benefit, or patient outcomes. The listed adverse-event counts likewise do not establish causation, and there is no randomized treatment comparator with which to assess relative safety or efficacy.

As a general statistical principle, a completed study can inform a question only to the extent that its methods and results are available and interpretable. Here, the design and endpoint are described, but important results and analysis details are absent. The record should therefore be read as a description of the study and its reported counts, not as evidence for a treatment effect or a definitive safety conclusion.

13. Why This Trial Matters Statistically

This study is statistically notable because it frames a pharmacokinetic question across pediatric age groups rather than relying on a single pooled description. The age-specific structure can make it possible to report clearance estimates separately for younger children, school-age children, and adolescents. Such estimates could be useful for describing how drug disposition varies across the studied groups, provided the results and analysis details are available.

The record also illustrates the distinction between a study’s design and the calculations sometimes used to plan later studies. This trial is recorded as a non-randomized, single-group study, whereas the associated planning assumptions describe equal allocation between two arms. Planning illustrations under different assumptions do not convert the original study into a comparative trial and do not represent observed power.

There is also a practical lesson in interpreting registry records: a defined endpoint is not the same as a reported result. The endpoint, summary statistic, analysis population, and assessment window are described, but the clearance values and their uncertainty are not reported in the registry record. Without those elements, readers cannot assess the principal pharmacokinetic finding.

Finally, the record’s outcome list and analysis count do not provide a multiplicity plan or explain how missing observations were handled. These are important parts of statistical interpretation, especially when several types of outcome are listed. The study’s value for statistical appraisal depends not only on its design but also on accessible results and transparent analysis methods.

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 main limitation for interpretation is that the primary endpoint results are not reported in the registry record. The median plasma clearance estimates, inter-quartile ranges, analysis denominators, and confidence intervals are unavailable, preventing assessment of the magnitude and precision of the primary outcome.

The study is described as non-randomized and single-group, with no comparator. Its age groups are not randomized treatment arms, so they cannot support a like-for-like treatment comparison. The record does not report adjustment for participant characteristics or a model for age-group comparisons.

Enrollment was 140, while the combined adverse-event group lists 138 participants at risk. The record does not explain this difference or state how many participants contributed to the final pharmacokinetics analysis set. Eligibility details, missing-data methods, and sensitivity analyses are not reported in the registry record.

Although 18 outcome measures are listed, the record lists 0 analyses and does not report a multiplicity approach. Results for the secondary imaging and lesion outcomes are also not reported in the registry record. The available adverse-event counts lack confidence intervals and further detail about attribution, timing, and event-level recurrence. Death counts are not reported in the registry record.

These limitations mean that the registry information supports a description of the study design and selected event counts, but not a complete statistical evaluation of pharmacokinetics, imaging outcomes, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Magnetic Resonance Imaging (MRI) With Gadavist in Children — NCT00468819.
• Registry record last updated 2015-07-22; status last verified 2015-06.
• Results first posted 2011-09-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, phase 1, open-label, multicenter, non-randomized, single-group study of gadobutrol for MRI in children and adolescents. Enrollment was 140. Participants received a single intravenous bolus of 0.1 mmol/kg body weight, equivalent to 0.1 mL/kg body weight.

The primary endpoint was median plasma clearance in L/h by age group, from injection up to 8 hours after injection, in the final pharmacokinetics analysis set. Clearance estimates and inter-quartile ranges are not reported in the registry record. The record lists 18 outcome measures and 0 analyses.

Adverse-event counts are reported for three age groups and a combined age 2 to 17 years group. The record does not describe a randomized comparator, report the primary endpoint results, or provide detailed missing-data and multiplicity methods.