Renal Safety Evaluation After Dotarem®-Enhanced MRI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Renal Safety Evaluation After Dotarem®-Enhanced MRI (NCT00650845), a non-randomized phase 4 study. The primary outcome is Number of Patients Presenting Contrast-induced Nephropathy as Defined by an Increase in Serum Creatinine Levels of a Least 25% Over Baseline Levels, in the Full Analysis Set Population..

2. Clinical Question

The question concerns a short-term laboratory change following imaging, rather than a longer-term clinical outcome. Serum creatinine is used in the endpoint definition to identify a specified increase from each patient's baseline level. That makes the primary outcome a binary event: each eligible participant either meets the threshold or does not. The registry also lists secondary outcomes based on percent change in serum creatinine and estimated glomerular filtration rate (eGFR), measured from baseline to 72±24 hours after examination. Those outcomes are specified for the Full Analysis Set or the Per Protocol Population, depending on the measure.

The clinical comparison is observational rather than randomized. The registry does not report how patients came to receive one type of MRI rather than the other, or whether the groups differed in factors that could affect kidney measurements. Consequently, the intended question can be described, but a causal interpretation of any difference would require caution. In addition, the primary event results are not reported in the registry record, so the size and precision of any observed difference cannot be described.

3. Trial Design

This was a Phase 4, parallel-group study with non-randomized allocation and no masking. It compared patients undergoing Dotarem®-enhanced MRI with patients undergoing non-enhanced MRI, both for diagnostic purposes. The record lists renal insufficiency as the condition and identifies Guerbet as the sponsor. The study status is completed. Its start is recorded as 2008-01, and primary completion is recorded as 2011-05.

The registry reports enrollment of 135 participants. That is the total enrollment figure, not necessarily the number with data for every endpoint. For the primary endpoint, the Full Analysis Set is defined as included patients who had both pre-procedure and post-procedure creatinine samples. The registry does not report the number analyzed for that endpoint. The adverse-event records separately list 70 participants at risk in the Dotarem®-enhanced MRI group and 44 in the non-enhanced MRI group; those safety denominators should not be mistaken for the primary endpoint analysis counts.

Because allocation was not randomized, group membership may reflect clinical or practical decisions rather than chance assignment. The registry does not report the allocation process, eligibility criteria in detail, baseline characteristics by group, or reasons patients received one examination rather than the other. The record itself flags that the arms are not a like-for-like control comparison. No masking was used, so treatment assignment was not concealed from participants or study personnel as described by the registry.

The registry gives the primary endpoint as the number of patients with a creatinine increase of at least 25% over baseline in the Full Analysis Set. The measurement timeframe is described as baseline before MRI and 3 days after MRI; the secondary outcome descriptions use 72±24 hours after examination. The secondary outcomes include percent change in serum creatinine and eGFR in the Full Analysis Set, plus variation in these measures in the Per Protocol Population. The registry record does not report the trial's statistical analysis plan, a sample-size justification, whether interim analyses were planned, or detailed procedures for handling missing measurements.

Although the record identifies a completed study and lists the endpoints and some safety counts, it does not report the primary endpoint results. It also does not report the results for the listed secondary outcomes. Therefore, the design and intended measurements can be described, but the efficacy or renal-safety comparison based on the primary laboratory endpoint cannot be reconstructed 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.

Before assignment: 10 patients were screened but did not undergo the planned procedure: 7 were screen failures and 3 were included but dropped out prior to undergoing the planned procedure. Hence the total number of patients who were assigned to both groups is 132.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set population: all included patients with a pre and post-procedure blood sample for creatinine measures.

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 Number of Patients Presenting Contrast-induced Nephropathy as Defined by an Increase in Serum Creatinine Levels of a Least 25% Over Baseline Levels, in the Full Analysis Set Population., measured over baseline pre MRI and 3 days post MRI.

The primary endpoint counts patients whose serum creatinine increased by at least 25% from baseline after MRI. It is recorded as a number of patients in the Full Analysis Set. A participant is counted as having the event if the post-examination measurement meets or exceeds that threshold relative to baseline; otherwise, the participant is not counted as having the event. The registry defines the Full Analysis Set as included patients with both pre-procedure and post-procedure blood samples for creatinine measurement.

The endpoint uses measurements made before MRI and about 3 days afterward. The registry's primary timeframe is stated as baseline before MRI and 3 days post MRI, while its secondary outcome descriptions specify 72±24 hours after examination. This endpoint focuses on a short-term change in a laboratory marker and applies the same threshold definition to both study groups.

In general, a threshold-based endpoint turns a continuous measurement into an event count. This can make the outcome straightforward to interpret as the number of participants crossing a prespecified boundary, but it also means that changes below the threshold are not counted as primary events. The registry lists secondary measures of percent change in creatinine and eGFR, which would describe laboratory changes without relying only on the primary event threshold.

The primary endpoint is relevant to the stated safety question because the study aimed to compare the frequency of a creatinine increase after contrast-enhanced and non-enhanced MRI. However, the registry record does not report the number of primary events in either group, a group comparison, or an uncertainty estimate. The endpoint definition alone therefore does not establish how often the event occurred or whether the observed frequency differed between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary: a patient either meets the serum-creatinine threshold or does not. The registry defines an event as an increase of at least 25% over baseline and specifies a patient count for each group. For a binary endpoint, common descriptive summaries include event counts and the number of participants assessed. Comparative summaries can express the difference in event proportions or a relative comparison. These are general statistical approaches; the registry record does not report which comparative measure or statistical test was used.

What does a threshold-based endpoint capture?

A threshold provides a consistent rule for classifying participants and can be useful when the clinical question concerns how many people cross a defined boundary. In this study, the boundary is a creatinine increase of at least 25% from baseline. Converting a continuous measurement into a binary event has a trade-off: it makes event counts easy to state, but it does not retain the full size of changes among participants who remain below the boundary. The listed secondary outcomes based on percent change in creatinine and eGFR address continuous change in a different way, though their results are not reported in the registry record.

Using a change from baseline also makes the baseline measurement important. The event classification depends on both the pre-examination and post-examination values. The registry's Full Analysis Set definition requires both samples. If either value is missing, the record's stated definition does not include that participant in this analysis population. The registry does not report how many participants had both samples, how missing measurements were handled beyond that population definition, or whether any imputation was used.

Why does the study design affect interpretation?

Random allocation is a general method for making treatment groups comparable on average with respect to measured and unmeasured characteristics. This study was non-randomized, and the registry explicitly cautions that the comparison is not like-for-like. If characteristics that influence both the MRI choice and subsequent creatinine measurements differ between groups, an unadjusted comparison can mix those influences with any contrast-related association. The record does not report detailed group characteristics, an adjustment strategy, or the statistical model used. It is therefore not possible to determine from the registry record whether or how potential confounding was addressed.

No masking was used. In general, masking can reduce some forms of bias in outcome assessment or study conduct, depending on the outcome and procedures. The primary outcome is based on laboratory measurements, but the registry record does not describe laboratory procedures, assessor blinding, or other safeguards. No further conclusion about bias control can be drawn from the masking field alone.

What do precision measures communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect under a specified analysis. A narrow interval indicates greater precision than a wider interval, while the interval's location helps show which effect sizes remain compatible with the data and assumptions. For a group comparison, the interval is most informative when paired with a clearly defined effect measure and outcome denominators. No primary endpoint estimate or confidence interval is reported in the registry record.

A p-value is also an analysis result, not a measure of effect size. In general, it describes how unusual the observed data would be under a particular null hypothesis and model assumptions. A small p-value does not establish causality, clinical importance, or the probability that the null hypothesis is true. The registry record does not report a primary endpoint p-value or specify the test used.

What can be said about planning calculations?

The registry record does not report the trial's own sample-size justification. A planning illustration associated with the posted analysis uses a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Such planning figures are hypothetical requirements under chosen assumptions, not observed results and not observed power. The registry does not report a trial-specific justification, and the primary observed effect is not reported in the registry record, so the illustration cannot supply evidence about the result.

General sample-size calculations depend on assumptions about the event rate, effect size, allocation, significance level, and desired power. If those assumptions differ from the data-generating conditions, the calculated number may not describe the study's actual ability to estimate the effect. In a non-randomized study, larger numbers do not by themselves remove systematic differences between groups. Precision and bias are distinct concerns: more observations may improve precision while leaving confounding unresolved.

How should the adverse-event counts be read?

The registry records serious adverse-event counts and other adverse-event counts for separate denominators. Counts describe how many participants are recorded in each category; they do not alone describe event severity beyond the category label, timing, recurrence, or causal relation to MRI. The listed serious adverse-event counts are zero in both groups, while other adverse events are recorded for 6 participants in the Dotarem®-enhanced MRI group and 0 in the non-enhanced MRI group. The record does not provide terms for those other events or death counts. These safety entries should not be substituted for the primary creatinine endpoint, whose results are absent.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Dotarem®-Enhanced MRI", "Non-enhanced MRI")
n      <- c(70, 44)
events <- c(1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dotarem®-Enhanced MRI  70  1  1.4  0.0  7.7  0.3  7.7  0.3  7.6
ARM  Non-enhanced MRI  44  0  0.0  0.0  8.0  -0.0  8.0  0.1  7.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including percent change in serum creatinine and eGFR, with some analyses assigned to the Full Analysis Set and others to the Per Protocol Population. The record does not report a multiplicity plan, such as whether the primary endpoint was designated as the sole confirmatory test, whether secondary outcomes were adjusted for multiple comparisons, or how the family of analyses was defined. When several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed without accounting for the number of tests. This is a general statistical concern, not evidence that any particular result was affected.

The registry does not report results for the primary or secondary outcomes, nor does it provide analysis-specific sample sizes, missing-data counts, or a detailed missing-data strategy. The primary Full Analysis Set requires both pre- and post-procedure creatinine samples. The Per Protocol Population is named for some secondary analyses, but its inclusion criteria and size are not reported in the registry record. These populations may therefore include different participants, and their estimates, if reported, would need to be interpreted in light of those definitions.

Missing outcome data can affect both the number of participants analyzed and the interpretation of an estimate. In general, excluding participants without paired measurements is straightforward to describe, but the resulting analysis can be biased if missingness is related to the outcome or to group assignment. Whether that concern applies cannot be assessed from the registry record. No imputation method, sensitivity analysis, or comparison of included and excluded participants is reported.

The total enrollment is 135, while safety records give separate at-risk denominators of 70 and 44. The registry does not report the primary endpoint denominators, so enrollment and safety counts should not be treated as the analysis population for the primary outcome. It is also not reported whether interim analyses were planned or conducted.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 serious adverse events among 70 participants at risk in the Dotarem®-enhanced MRI group and 0 among 44 participants at risk in the non-enhanced MRI group. These are the serious-event counts recorded for the two groups. Zero recorded events means no serious adverse events are listed in these entries; it does not establish that the groups have identical risks or rule out events that were not captured or reported.

For other adverse events, the registry lists 6 participants affected in the Dotarem®-enhanced MRI group and 0 in the non-enhanced MRI group. The record does not report the event terms, severity details, timing, recurrence, or whether events were judged related to the examination or contrast agent. Death counts are not reported in the registry record.

These safety counts are descriptive and use the stated at-risk denominators. They are distinct from the primary endpoint, which counts participants meeting a serum-creatinine threshold and whose results are not reported. Small or absent event counts also limit what can be inferred about uncommon outcomes. The counts alone do not provide a complete safety profile or a causal comparison between the non-randomized groups.

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

The record establishes that a completed Phase 4, non-randomized, parallel-group study was designed to compare Dotarem®-enhanced MRI with non-enhanced MRI in patients with renal insufficiency. It specifies a primary laboratory endpoint: the number of participants with at least a 25% increase in serum creatinine from baseline after MRI. It also records some adverse-event counts. These are useful details about the study's question and recorded safety data.

The record does not report the primary endpoint counts or a comparative estimate. It also does not report the results for the listed secondary changes in creatinine or eGFR. Consequently, the posted information cannot establish how often the primary event occurred, the size or direction of a group difference, or the precision of a comparison. The endpoint definition is not evidence that an event did or did not occur.

The adverse-event entries show no serious adverse events recorded in either group and list other adverse events for 6 participants in the Dotarem®-enhanced MRI group and 0 in the non-enhanced MRI group. The event details are not reported, and these counts do not answer the primary creatinine question. They also do not, by themselves, prove a causal relationship or establish a difference in underlying risk.

Even if comparative outcome estimates were available, the non-randomized allocation would matter. The registry warns that the groups are not a like-for-like control comparison, and it does not report enough information about group characteristics or adjustment methods to assess comparability. In general, observed differences in a non-randomized study can reflect both the exposure under study and pre-existing differences between participants.

Accordingly, the record supports a description of the intended endpoint, design, enrollment, and listed adverse-event counts, but not a conclusion about the comparative primary outcome. It does not report a sample-size justification or statistical analysis plan. Readers should distinguish the short-term laboratory endpoint from longer-term clinical outcomes, which are not reported as results in the registry record.

14. Why This Trial Matters Statistically

This study raises a statistically important question because its primary outcome is based on a defined change in a laboratory measure after imaging. The threshold of at least a 25% increase in creatinine makes the event rule explicit, while the listed secondary outcomes retain information about changes in creatinine and eGFR. Together, these endpoints illustrate the difference between asking how many people cross a threshold and describing the size of continuous changes.

The non-randomized design is central to interpreting the intended comparison. Randomization is one way to reduce systematic differences between groups; it was not used in this study. The registry itself warns that the arms are not a like-for-like control comparison. That warning underscores a broader lesson: statistical uncertainty around an estimate does not account for all possible bias. A confidence interval can describe sampling uncertainty under an analysis, but it cannot by itself correct confounding or make groups comparable.

The record also illustrates why outcome reporting matters. Knowing the endpoint definition and study enrollment is not enough to evaluate the result. The primary event counts, analysis denominators, comparative estimate, and precision are not reported in the registry record. Without them, readers cannot assess the observed frequency or magnitude of a difference. Safety counts provide some information, but do not replace the primary outcome or a complete account of adverse-event details.

Finally, the distinction between planned analyses and observed evidence is important. The record does not report a trial-specific sample-size justification or analysis plan. Planning calculations are hypothetical and depend on assumptions; they cannot be treated as observed power or as evidence about an unreported result. This case therefore highlights how design, endpoint definition, analysis populations, missing data, and completeness of results all shape what can be concluded from a clinical trial record.

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 most direct limitation is that the registry record does not report the primary outcome results. It gives the threshold definition and population criteria, but not the event counts, analysis denominators, group comparison, or precision estimate. Results for the listed secondary outcomes are also not reported. This prevents quantitative interpretation of the study's central renal-safety question.

The study is non-randomized, and the registry explicitly states that the arms are not a like-for-like control comparison. The record does not describe the allocation process, reasons for choosing each MRI approach, detailed baseline characteristics, or adjustment methods. Potential group differences therefore cannot be evaluated from the reported information. No masking was used, and the registry does not describe procedures for blinded assessment or laboratory handling.

The primary analysis population requires pre- and post-procedure creatinine samples, but the number meeting that definition is not reported. The registry also names a Per Protocol Population for some secondary outcomes without reporting its size or detailed definition. Missing-data counts and methods are not reported, so the effect of incomplete measurements cannot be assessed.

Although the total enrollment is 135, safety denominators are separately reported as 70 and 44. These safety figures do not establish the primary endpoint analysis sizes. The record does not report a trial-specific sample-size justification, statistical analysis plan, multiplicity procedure, or interim-analysis information. These omissions limit assessment of the planned inferential framework. Finally, adverse-event details beyond the participant counts are sparse: terms and causal attribution are not reported, and death counts are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Renal Safety Evaluation After Dotarem®-Enhanced MRI — NCT00650845.
• Registry record last updated 2015-06-09; status last verified 2015-03.
• Results first posted 2015-06-09.
• 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.

19. Record Summary

The registry describes a completed Phase 4, non-randomized, unmasked, parallel-group study of Dotarem®-enhanced versus non-enhanced MRI in patients with renal insufficiency. Enrollment was 135. The primary endpoint was the number of patients in the Full Analysis Set with a serum creatinine increase of at least 25% over baseline after MRI.

The primary and secondary outcome results are not reported in the registry record. Safety entries list 0 serious adverse events among 70 participants at risk in the Dotarem®-enhanced MRI group and 0 among 44 in the non-enhanced MRI group. Other adverse events are listed for 6 participants and 0 participants, respectively. The registry cautions that the non-randomized arms are not a like-for-like control comparison.