Efficacy and Safety of Gadopiclenol for Body Magnetic Resonance Imaging (MRI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Gadopiclenol for Body Magnetic Resonance Imaging (MRI) (NCT03986138), a randomized phase 3 study. The primary outcome is Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI.

2. Clinical Question

The clinical question is about image-based assessment, not a clinical outcome such as symptoms or subsequent health events. Three independent readers rated the specified visualization criteria, using a four-point scale. The crossover design also allowed comparison with gadobutrol-enhanced imaging, but the primary endpoint named in the registry record is the comparison with unenhanced imaging. These comparisons should therefore be kept distinct when interpreting the trial.

3. Trial Design

This was a Phase 3 randomized, quadruple-masked crossover trial sponsored by Guerbet. The registry record lists an enrollment of 324 and a completed status. The recorded start date is 2019-08-27, and the primary completion date is 2020-12-09. The condition listed is lesion in a body region.

The two treatment sequences were gadopiclenol-enhanced MRI followed by gadobutrol-enhanced MRI, and gadobutrol-enhanced MRI followed by gadopiclenol-enhanced MRI. Thus, the trial included both contrast agents in each sequence, with the order varying. For the second sequence described in the primary endpoint timeframe, gadopiclenol imaging was performed 2-14 days after gadobutrol-enhanced MRI. The interval between examinations in the other sequence is not reported in the registry record.

In a crossover study, each participant serves as a source of observations under more than one treatment condition. In general, this can support within-participant comparisons, because stable characteristics shared across examination periods do not vary between the participant’s own observations. It also makes sequence, examination period, and the spacing between examinations relevant considerations. The registry record identifies the crossover structure and gives one sequence-specific timing detail, but further protocol information on period effects or carryover is not reported.

The record states quadruple masking, but does not describe which groups of people were masked or how masking was implemented. It also does not report the randomization procedure, allocation concealment, or details of the statistical analysis plan. Those aspects cannot be inferred from the design labels alone.

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: Among the 324 screened patients,19 were screen failure, 1 received the first contrast agent but was not randomized. A total of 304 patients were randomized, of whom 300 (151 in Arm 1 and 149 in Arm 2) received the first contrast agent and underwent the first MRI (First MRI Period). After a washout period of 2-14 days, 277 patients (141 in the Arm 1 and 136 in the Arm 2) received the second contrast agent and underwent the second MRI (Second MRI Period). 275 patients completed the study.

First MRI Examination

Reasons for not completing this period:

Washout

Reasons for not completing this period:

Second MRI Examination

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included a total of 278 patients who had both Pre and Paired images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 145 patients in the Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 133 patients in the Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (per patient).

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.

Population: The analysis was based on participants. For the primary analysis to demonstrate the superiority of gadopiclenol-enhanced MRI compared to unenhanced MRI, the analysis population was patients who had both Pre (unenhanced) and Paired (combined unenhanced and contrast-enhanced) images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 145 patients of Arm 1 who performed first MRI and 133 patients of Arm 2 who performed second MRI.

6. Primary Endpoint

The registry lists the primary outcome as Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI, measured over At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI..

The primary endpoint concerns lesion visualization on gadopiclenol-enhanced MRI compared with unenhanced imaging. It uses the mean of a score per patient for each of three co-primary criteria: border delineation, internal morphology, and degree of contrast enhancement. Three independent readers assessed the images. For each criterion, readers could score up to three of the most representative matching lesions using a four-point scale, ranging from poor or none to excellent. Scores for a patient and criterion were averaged across the lesions scored.

The registry description defines the patient-level difference as the difference between scores on paired unenhanced and contrast-enhanced images and scores on pre-contrast unenhanced images. A score difference is intended to express the change in rated visibility associated with contrast-enhanced imaging, while retaining separate information for each criterion and reader. The outcome is continuous in the sense that it is a mean score, even though the underlying ratings use ordered scale categories.

These criteria capture different visual properties of a lesion. Border delineation addresses how clearly its edge is seen; internal morphology addresses its internal appearance; and degree of contrast enhancement addresses the assessed contrast. Together they describe image visualization rather than a direct measure of diagnosis, patient health, or treatment benefit. The registry record does not report the resulting primary estimates, so the size and precision of any observed differences are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean score represent?

The endpoint begins with reader ratings on a four-point scale for each visualization criterion. For a given patient and criterion, the described score is the mean across the matching lesions that were scored, up to three. The analysis then considers the difference between ratings from paired contrast-enhanced and pre-contrast images. A mean summarizes the ratings into a continuous measure, allowing the comparison to be expressed as an average change in score rather than as a separate category count for every rating.

As a general statistical matter, taking a mean is a compact summary, but it can conceal variation. Participants may have different numbers of lesions scored, and scores may differ across readers or criteria. The registry record explains the scoring approach but does not report distributions, variability across participants, or how multiple reader assessments were combined in the final analysis.

Why is the crossover structure important?

In general, crossover data include repeated observations from the same participant under different conditions. These observations are related, so an analysis should account for within-participant pairing. Treating paired observations as independent can misrepresent uncertainty. A paired analysis uses the relationship between each participant’s observations; a model-based analysis may also include examination period or sequence, depending on the prespecified plan.

The registry identifies two treatment orders and describes a 2-14 day interval before the gadopiclenol examination for participants receiving gadobutrol first. The analytical model, handling of period effects, and assessment of carryover are not reported in the registry record. A crossover label alone does not reveal how those issues were handled.

What do standard errors and confidence intervals convey?

The primary outcome lists the least-squares mean as its parameter and standard error as its dispersion measure. In general, a least-squares mean is a model-based mean, often adjusted for terms included in the analysis model. The standard error describes the estimated uncertainty of an estimate across repeated samples under the model. A standard error is not the spread of individual patient scores.

A confidence interval uses an estimate and its uncertainty to give a range of values compatible with the data under specified assumptions. A narrow interval conveys greater precision than a wide interval. Whether an interval excludes a reference value may be relevant to a statistical test, but interpretation also depends on the scale, analysis, and clinical question. No least-squares means, standard errors, confidence intervals, or primary p-values are reported in the registry record, so these quantities cannot be interpreted for this trial.

How should reader and criterion results be considered?

The assessment involved three independent readers and three co-primary criteria. In general, multiple readers can provide information on whether an image-based assessment is consistent across evaluators. But reader assessments may be correlated because they evaluate the same images, and a statistical method should reflect the structure of the data. The registry description does not state whether the final inference combined readers, analyzed them separately, or used another approach.

Multiple co-primary criteria also create a multiplicity question. In general, testing several endpoints can increase the chance of at least one apparently positive result if no adjustment or decision rule is used. A prespecified hierarchy, adjustment, or joint decision rule can address this issue, but no such procedure is described in the registry record. The number of analyses listed is 18; that fact alone does not reveal which tests were confirmatory, whether they were related, or how multiplicity was handled.

What can planning calculations say?

In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, allocation, and a statistical testing approach. It is not a measure of the probability that a completed trial has demonstrated an effect. Planning illustrations based on an observed effect are also not a substitute for the trial’s prespecified design justification. The registry record does not report the trial’s sample-size justification or the assumptions used to plan enrollment.

The record’s planning description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. It characterizes these as planning illustrations, not the trial’s own design. The observed primary effect is not reported in the registry record, and the record does not provide a primary comparison from which to interpret such illustrations. Sample-size outputs should therefore be understood as hypothetical planning quantities, not observed power or evidence of an outcome.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described using three co-primary criteria: border delineation, internal morphology, and degree of contrast enhancement. The record also describes assessments by three independent readers and lists a secondary outcome comparing gadopiclenol-enhanced MRI with gadobutrol-enhanced MRI. These features create several potential result dimensions. In general, when multiple hypotheses are tested, a prespecified approach is needed to explain how the overall chance of false-positive findings is controlled or how results are prioritized.

The registry record does not report a multiplicity adjustment, hierarchy, joint success rule, or other decision procedure for the co-primary criteria, readers, or secondary comparison. The listed 18 analyses do not by themselves show how many were confirmatory or how their results were interpreted. The sponsor’s statistical plan and any interim analyses are not reported in the registry record.

The Full Analysis Set is described as including 278 participants with both pre-contrast and paired gadopiclenol images assessable for primary criteria for at least one matching lesion for at least one off-site reader. This criterion clarifies that the primary analysis population required usable paired imaging information, but the registry description is truncated after beginning a sequence-specific breakdown. The full population description is therefore not reported in the registry record.

The record does not explain how missing or non-assessable images, missing reader scores, or incomplete examinations were handled. It does not report whether missingness was addressed through imputation, exclusion, or another method, or whether sensitivity analyses were conducted. In general, missing-data handling can affect an estimate if the availability of observations is related to the values that would otherwise have been measured. Without those details, the robustness of the primary analysis to missing or unassessable imaging cannot be evaluated.

11. Safety Results

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

Deaths

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: condition aggravated (0.3%), depressed level of consciousness (0.3%), covid-19 (0.3%).

The registry record reports serious adverse-event figures for the two treatment groups. In the gadopiclenol group, 288 were at risk and 3 were affected; in the gadobutrol group, 290 were at risk and 0 were affected. The record reports zero deaths in both groups. Other adverse events were recorded for 50 in the gadopiclenol group and 58 in the gadobutrol group, with 288 and 290 at risk, respectively.

These are descriptive group figures. The registry record does not report a statistical comparison, confidence intervals, or further details about the adverse-event analysis. A count of affected participants is not necessarily equivalent to a count of all event episodes, and the record does not specify in these figures whether multiple events in one participant were counted separately. The crossover design also means that the relationship between treatment exposure and event attribution requires the analysis details, which are not reported.

The most frequent serious-event terms listed are Condition Aggravated, Depressed Level Of Consciousness, and Covid-19, each reported as 0.3%. These terms are descriptive entries; the record does not provide enough context to interpret their clinical circumstances. Counts and listed terms can describe what was recorded, but they do not alone establish a comparative safety effect.

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

The trial record describes a randomized, quadruple-masked crossover evaluation of gadopiclenol and gadobutrol for body MRI. Its primary imaging question compares lesion visualization on gadopiclenol-enhanced images with unenhanced images, using scores for border delineation, internal morphology, and degree of contrast enhancement. It also identifies a secondary comparison with gadobutrol-enhanced MRI.

What the record does not provide is the primary result in numerical form. There is no reported estimate of the mean score difference, no standard error or confidence interval, and no primary p-value. Without those quantities, the size, direction, and precision of the primary comparison cannot be judged from the registry record. The endpoint description explains what was intended to be measured, not what the results were.

The results should not be interpreted as a direct assessment of diagnosis, patient outcomes, or long-term clinical effects. The endpoint is based on reader ratings of MRI images. A change in a visualization score, if reported, would need to be interpreted on that score’s scale and in relation to the study’s analysis and clinical context. No such estimate is reported in the registry record.

The safety counts describe recorded events in the listed groups, including serious adverse events, other adverse events, and deaths. They are not a complete basis for estimating comparative risk without definitions, follow-up details, exposure handling, and an inferential analysis. The record does not report those details.

In general, a randomized design can support a more credible treatment comparison than an uncontrolled design, while crossover studies can use within-participant comparisons. Those advantages depend on appropriate execution and analysis, including consideration of sequence and period. The registry record does not provide enough statistical-plan detail to assess those features fully. Accordingly, the design and endpoint are identifiable, but the central comparative result and its uncertainty are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises statistical issues common to imaging studies. The outcome is based on structured reader assessments rather than a single direct measurement. Each patient-level score averages ratings across matching lesions, and the endpoint is assessed by independent readers. That structure makes it important to distinguish variation between patients, lesions, and readers, and to know how those sources of variation entered the analysis.

The crossover design is another important feature. In general, it can make within-participant comparisons informative because the same participant contributes observations under different conditions. It also makes the data dependent and places importance on treatment order and examination period. The registry gives the two treatment sequences and some timing information, but does not report the model used to handle the paired structure or possible period-related effects.

The three co-primary criteria make multiplicity relevant. A reader needs to know whether success required a result on every criterion, any one criterion, or a specified combination, and whether the analysis adjusted for multiple testing. The registry record does not report such a rule. This limits interpretation even if criterion-specific findings were available, and the primary findings themselves are not reported.

Finally, transparent reporting of estimates and uncertainty is central to statistical interpretation. Endpoint definitions and safety counts help clarify what was measured, but they cannot substitute for effect estimates and confidence intervals. The missing primary estimate means that the record allows readers to assess the study’s measurement framework and design features, but not the precision or magnitude of its main imaging comparison.

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 principal limitation for interpreting the registry record is that it does not report the primary-outcome estimates or their uncertainty. The primary endpoint is defined in detail, but no mean differences, standard errors, confidence intervals, or p-values are reported. This prevents quantitative assessment of the primary imaging comparison.

The endpoint has multiple co-primary criteria and uses ratings from three independent readers. The record does not report how reader observations were combined, whether results were presented separately by reader, or what rule governed interpretation across the criteria. It also does not describe a multiplicity procedure. The number of listed analyses does not resolve these uncertainties.

The registry describes a Full Analysis Set of 278 participants meeting an assessability criterion, but its sequence-specific population description is incomplete. It does not explain the disposition of participants outside that set, the handling of non-assessable images, or the treatment of missing scores. This limits assessment of how the analysis population relates to enrollment and whether missing data could influence the results.

Although the trial is identified as randomized, quadruple-masked, and crossover, the record does not report the randomization method, masking implementation, analysis model, or handling of treatment sequence and period. The interval of 2-14 days is stated for one gadopiclenol examination sequence; further timing details are not reported in the registry record.

Safety interpretation is also limited by the absence of comparative uncertainty measures and detailed event-analysis methods. The figures are descriptive and do not by themselves establish differences between treatments. Further protocol details, the sample-size justification, and any interim analyses are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Gadopiclenol for Body Magnetic Resonance Imaging (MRI) — NCT03986138.
• Registry record last updated 2025-10-27; status last verified 2025-09.
• Results first posted 2025-10-27.
• 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

NCT03986138 is a completed Phase 3 randomized, quadruple-masked crossover trial sponsored by Guerbet. It enrolled 324 participants with a lesion in a body region. The recorded start date is 2019-08-27, and the primary completion date is 2020-12-09.

The trial compared gadopiclenol-enhanced MRI and gadobutrol-enhanced MRI in two treatment sequences. Its primary endpoint assessed lesion visualization on gadopiclenol-enhanced versus unenhanced images, using three criteria rated by independent readers. The Full Analysis Set described for primary assessment included 278 participants meeting an image-assessability criterion.

The registry record reports descriptive adverse-event counts, including serious events and deaths, but does not report the primary endpoint estimates or their uncertainty. Details of the statistical plan, multiplicity handling, and missing-data methods are not reported in the registry record.