This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Crossover Comparison of MultiHance and Dotarem (NCT02070380), a randomized phase 4 study. The primary outcome is Global Diagnostic Preference Between the Two Exams.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02070380 |
| Phase | Phase 4 |
| Condition | Brain Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 179 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bracco Diagnostics, Inc |
| Results posted | Yes |
2. Clinical Question
Population
Patients with brain tumors were the intended study population. The registry lists brain disease as the condition and records enrollment of 179 participants. The primary endpoint description concerns the 159 patients who had post-dose exams for both MultiHance doses and Dotarem. The per-protocol population was more specifically defined as patients who completed both exams, had global paired image data available, and had no major protocol violations.
Intervention
The imaging comparison included MultiHance at 0.1 mmol/kg and at 0.05 mmol/kg. Each was compared with Dotarem at 0.1 mmol/kg. The trial used a crossover arrangement, so the registry describes sequences in which participants received the contrast agents in different orders.
Comparator
Dotarem at 0.1 mmol/kg was the comparator for each MultiHance dose. The primary endpoint compared image sets from MultiHance and Dotarem exams. Those image sets were obtained within 2 to 14 days.
Primary question
For each of 3 blinded readers, did the reader prefer the images after MultiHance, prefer the images after Dotarem, or consider the images from both exams equal? A reader could exclude an image set deemed technically inadequate from that reader’s efficacy assessment.
The registry summary says the study aimed to show superiority of MultiHance. That statement describes the study’s stated aim, not an observed result. The registry record does not report how many assessments fell into each preference category, or a comparative estimate demonstrating the direction or size of any preference. The posted information therefore establishes the question and the design, but not an answer about which contrast agent readers preferred.
3. Trial Design
This was a Phase IV, randomized, triple-masked, multi-center study with a crossover model. The registry records enrollment of 179 participants and a completed status. The recorded study start was 2014-02, and primary completion was 2015-03. Those dates describe the registry record; they do not provide details about the timing of individual participant visits.
The crossover sequences paired MultiHance at 0.1 mmol/kg with Dotarem at 0.1 mmol/kg, or MultiHance at 0.05 mmol/kg with Dotarem at 0.1 mmol/kg. The arm descriptions include both possible orders for each dose pairing: MultiHance followed by Dotarem and Dotarem followed by MultiHance. The registry therefore indicates that treatment order varied, but does not report the sequence allocation counts or the method used to generate the randomization sequence.
In general, a crossover design compares treatments within participants, which can reduce the influence of stable differences between participants. It also makes the validity of the comparison dependent on features such as period effects, carryover, and the analysis of paired observations. The washout interval, any assessment of carryover or period effects, and the statistical handling of sequence are not reported in the registry record. The primary outcome description states that the image sets were obtained within 2 to 14 days; it does not specify whether that interval was the washout period.
Three blinded readers assessed the image sets. The registry identifies the study as triple-masked, but does not state which participant, investigator, reader, or other roles were masked. It also does not describe the masking procedure. The endpoint analysis was based on the per-protocol population as defined in the registry. Enrollment, the number with paired post-dose exams, and the analysis population are distinct quantities, and the registry does not report a full participant flow explaining the differences among them.
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: 179 patients were enrolled and signed informed consent. Each enrolled patient was randomized and 177 were dosed with at least one contrast agent.
First Injection
| Stage | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg |
|---|---|---|---|---|
| STARTED | 31 | 39 | 53 | 54 |
| COMPLETED | 31 | 39 | 53 | 54 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Washout (no Second Injection/MRI)
| Stage | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg |
|---|---|---|---|---|
| STARTED | 31 | 39 | 53 | 54 |
| COMPLETED | 31 | 34 | 51 | 51 |
| NOT COMPLETED | 0 | 5 | 2 | 3 |
Reasons for not completing this period:
| Reason | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg |
|---|---|---|---|---|
| Withdrawal by Subject | 0 | 5 | 2 | 3 |
Second Injection
| Stage | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg |
|---|---|---|---|---|
| STARTED | 31 | 34 | 51 | 51 |
| COMPLETED | 31 | 32 | 50 | 46 |
| NOT COMPLETED | 0 | 2 | 1 | 5 |
Reasons for not completing this period:
| Reason | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg |
|---|---|---|---|---|
| Image sets missing or technically inadeq | 0 | 1 | 0 | 0 |
| Protocol Violation | 0 | 1 | 1 | 5 |
Analysis population for the primary outcome, as defined in the registry: Per Protocol=patients who completed both exams, had global paired image data available, and had no major protocol violations
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.
| Characteristic | Unit | MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 31 | 32 | 50 | 46 | 159 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 24 | 20 | 36 | 28 | 108 |
| Age, Categorical: >=65 years | Participants | 7 | 12 | 14 | 18 | 51 |
| Gender: Female | Participants | 20 | 20 | 25 | 22 | 87 |
| Gender: Male | Participants | 11 | 12 | 25 | 24 | 72 |
| Race/Ethnicity, Customized: White | participants | 31 | 31 | 46 | 46 | 154 |
| Race/Ethnicity, Customized: Black | participants | 0 | 1 | 2 | 0 | 3 |
| Race/Ethnicity, Customized: Asian | participants | 0 | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Other | participants | 0 | 0 | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 12 | 15 | 21 | 21 | 69 |
| Region of Enrollment: Europe | participants | 19 | 17 | 29 | 25 | 90 |
6. Primary Endpoint
The registry lists the primary outcome as Global Diagnostic Preference Between the Two Exams, measured over Comparison of image sets obtained within 2 to 14 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participant exams |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was global diagnostic preference between the two exams. For each reader, the outcome distinguished preference for images after MultiHance, preference for images after Dotarem, and an assessment that the image sets were equal. The registry describes the unit as participant exams and gives the timeframe as a comparison of image sets obtained within 2 to 14 days.
This kind of reader-rated endpoint captures an overall judgment about the diagnostic appearance of paired image sets rather than a measurement of a single lesion feature. The registry lists secondary imaging outcomes including lesion border delineation, lesion internal morphology, extent of disease, lesion contrast enhancement, lesion to background ratio on post T1-weighed spin echo images, and lesion-brain contrast-to-noise ratio. These are distinct imaging assessments and should not be treated as interchangeable with the global preference endpoint.
In general, a preference endpoint can summarize a reader’s integrated assessment of image quality or diagnostic appearance. Its interpretation depends on the scoring categories, reader consistency, and the statistical treatment of paired assessments. The registry explains the categories and identifies 3 blinded readers, but does not report category counts, reader-specific estimates, uncertainty intervals, or a statistical test for the primary endpoint. It is therefore not possible from the registry record to quantify the observed preference or its precision.
A reader could exclude an image set judged technically inadequate. The number of assessments evaluated differed slightly across readers and endpoints as a result. This means that the analyzed observations need not have the same denominator for every reader or imaging measure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted registry information describes a randomized crossover comparison and defines a clinically interpretable reader judgment: preference for MultiHance images, preference for Dotarem images, or no preference. However, it does not report the number of assessments in those categories. No primary endpoint estimate, confidence interval, or p-value is reported in the registry record. The direction, magnitude, and precision of the reader preference therefore cannot be determined from the posted results.
The study’s stated aim was to show superiority of MultiHance. An aim is not evidence that the comparison met a superiority criterion. To evaluate such a claim, readers would need the prespecified comparison, the analyzed counts or estimates, an uncertainty measure, and the analysis population used. Those outcome results and statistical details are not reported in the registry record. The study’s aim should not be read as a finding.
The primary endpoint involved 3 blinded readers and assessments of paired image sets. In general, reader-specific results matter because a pooled summary can conceal disagreement among readers. In general, paired analyses should account for the relationship between observations from the same participant; treating paired observations as independent can misstate uncertainty. The registry does not report whether estimates were reader-specific, combined across readers, adjusted for within-participant pairing, or modeled to account for reader variation.
The registry reports that 159 patients had post-dose exams for both MultiHance doses and Dotarem. This does not mean that all 159 necessarily contributed to every reader’s endpoint analysis: technically inadequate image sets could be excluded for a particular reader, and the number evaluated differed slightly across readers and endpoints. The per-protocol definition also required completion of both exams, global paired image data, and no major protocol violations. A complete account of how many participants met each criterion is not reported in the registry record.
The registry lists 7 outcome measures and 42 analyses. A collection of outcomes and analyses can raise multiplicity concerns because repeated testing can increase the chance of a nominally notable result. In general, interpretation depends on whether the primary comparison was designated in advance and whether adjustment or a hierarchy was used. The registry does not report a multiplicity strategy or enough outcome results to assess how the analyses relate to one another.
The adverse-event entries report zero serious adverse events in each listed group. Other adverse events are also recorded, with counts differing among the listed groups. These are descriptive entries, not a complete comparative safety analysis: the registry does not provide event definitions, exposure-adjusted analyses, or a statistical comparison. The death counts are not reported in the registry record.
The listed planning assumptions describe sample-size illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence of a prespecified design justification. The trial’s own sample-size justification is not reported in the registry record.
9. Statistical Methods Explained
Statistical methods help connect an observed contrast to the uncertainty around it. For this trial, the registry describes the outcome categories, readers, crossover structure, and per-protocol population, but does not report the primary endpoint results or the statistical analysis plan. The explanations below are general; they do not describe methods confirmed to have been used for this trial.
What does a confidence interval communicate?
In general, a confidence interval expresses the uncertainty around an estimated treatment contrast under a stated statistical model. A narrow interval indicates greater precision than a wide interval, but precision alone does not establish clinical importance. The estimate and interval must be interpreted together, and the interval’s construction depends on the analysis method and assumptions. The registry record does not report a confidence interval for global diagnostic preference, so the precision of the primary comparison cannot be assessed from the posted results.
Why does the crossover structure matter?
In general, a crossover trial observes participants under more than one treatment condition. Because measurements from the same participant are related, a paired analysis can use within-participant comparisons and account for that dependence. An analysis that ignores pairing may give an inappropriate estimate of uncertainty. Crossover analyses may also need to consider treatment sequence, period effects, and carryover, since an earlier treatment or assessment period could influence later observations. The registry records different treatment orders but does not state how pairing, sequence, period, or carryover were handled analytically. The design label alone does not establish that these issues were addressed in a particular way.
How should reader assessments be considered?
In general, image ratings made by multiple readers can vary both because images differ and because readers may apply judgment differently. A reader-specific analysis can show whether the pattern is consistent across readers. A combined analysis may aim to represent an average across readers, but needs a method that accounts for the clustering or dependence created by repeated ratings. The registry identifies 3 blinded readers and says that their denominators differed slightly across readers and endpoints. It does not report reader-specific preference counts, reader agreement, or a statistical model for reader variability. Consequently, no claim about consistency among readers can be made from the registry record.
What do the outcome categories imply for analysis?
The primary endpoint is categorical: preference for MultiHance, preference for Dotarem, or equality. In general, a categorical outcome can be summarized with counts and proportions, while a comparative analysis may estimate a difference or another contrast between the categories. For paired categorical data, the method should reflect that the image sets are linked within a participant. The choice of estimand also matters: a reader-level preference, an average across readers, and a participant-level summary answer different questions. The registry does not report a primary contrast definition, the category counts, or the test used. No recalculated comparison is possible from the outcome details posted.
Why can over-dispersion matter?
In general, over-dispersion occurs when the variability in count data exceeds what a statistical model assumes. If a model assumes less variability than the data contain, standard errors can be too small and uncertainty can be understated. Methods that allow extra variability may be considered when the data structure and outcome support them. The primary endpoint is described as a number of participant exams across preference categories, but the registry does not report the underlying counts or the fitted model. There is no basis in the registry record to determine whether over-dispersion was present or whether it affected the analysis.
What does multiplicity mean for multiple analyses?
In general, testing several outcomes, comparisons, readers, or analysis populations creates multiple opportunities to observe a result that appears notable by chance. A statistical plan can control that risk through adjustment, a prespecified hierarchy, or another declared approach. The registry lists 7 outcome measures and 42 analyses, but the multiplicity method, any hierarchy, and the definition of the primary confirmatory comparison are not reported in the registry record. The count of analyses by itself does not establish that a particular adjustment was required or applied.
How should the sample-size illustrations be read?
The registry describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations define the effect to detect as a stated fraction of the observed effect. In general, such calculations ask what sample size would be needed under chosen assumptions; they do not show the probability that the completed trial detected a true effect. When based on an observed effect, they are especially dependent on that estimate and should not be treated as the trial’s original design justification. These figures are planning illustrations, not observed power. The registry record does not report the trial’s own sample-size justification.
For this endpoint, the registry does not report estimates, standard errors, confidence intervals, p-values, or a sufficiently detailed analysis plan. General statistical principles can clarify what those quantities would mean, but cannot substitute for the missing outcome results or establish which methods were actually used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures and 42 analyses. The primary outcome is global diagnostic preference; listed secondary outcomes include lesion border delineation, lesion internal morphology, extent of disease, lesion contrast enhancement, lesion to background ratio on post T1-weighed spin echo images, and lesion-brain contrast-to-noise ratio. The registry does not explain how the analyses were grouped, whether a hierarchy was prespecified, or whether any adjustment for multiple comparisons was used.
In general, multiplicity matters when several outcomes or contrasts are tested because repeated testing can make chance findings more likely. A prespecified primary analysis and a declared strategy for secondary analyses help readers distinguish confirmatory evidence from exploratory findings. The posted record does not report a multiplicity strategy, and it does not provide the primary category results or secondary outcome estimates. It is therefore not possible to judge the statistical evidence across the full set of analyses.
Missingness and exclusions also affect interpretation. The primary endpoint description states that image sets judged technically inadequate by a blinded reader were excluded from efficacy analysis for that reader. The number of participant exams evaluated differed slightly across readers and endpoints. The registry does not report the exact reader-specific denominators, reasons for technical inadequacy, or any sensitivity analysis for excluded assessments.
The per-protocol population required completion of both exams, available global paired image data, and no major protocol violations. The registry does not report a full account of exclusions, missing outcomes, or analyses in other populations. It also does not state how missing data were handled. These details are needed to assess whether the analyzed observations represent the randomized participants and whether exclusions could affect the comparison.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Study Arm 1 / MultiHance 0.1 mmol/kg | 0 | 65 | 0.0% |
| Study Arm 1 / Dotarem 0.1 mmol/kg | 0 | 70 | 0.0% |
| Study Arm 2/ MultiHance 0.05 mmol/kg | 0 | 104 | 0.0% |
| Study Arm 2 / Dotarem 0.1 mmol/kg | 0 | 105 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Study Arm 1 / MultiHance 0.1 mmol/kg | 1 of 65 |
| Study Arm 1 / Dotarem 0.1 mmol/kg | 2 of 70 |
| Study Arm 2/ MultiHance 0.05 mmol/kg | 3 of 104 |
| Study Arm 2 / Dotarem 0.1 mmol/kg | 7 of 105 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Study Arm 1 / MultiHance 0.1 mmol/kg | Study Arm 1 / Dotarem 0.1 mmol/kg | Study Arm 2/ MultiHance 0.05 mmol/kg | Study Arm 2 / Dotarem 0.1 mmol/kg |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 0 of 65 | 2 of 70 | 0 of 104 | 2 of 105 |
| Skin infection | Infections and infestations | 1 of 65 | 0 of 70 | 0 of 104 | 0 of 105 |
| Injection site swelling | General disorders | 0 of 65 | 0 of 70 | 0 of 104 | 1 of 105 |
| Injection site pruritus | General disorders | 0 of 65 | 0 of 70 | 0 of 104 | 1 of 105 |
| Procedural pain | Injury, poisoning and procedural complications | 0 of 65 | 0 of 70 | 1 of 104 | 0 of 105 |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 65 | 0 of 70 | 0 of 104 | 1 of 105 |
| Dizziness | Nervous system disorders | 0 of 65 | 0 of 70 | 1 of 104 | 0 of 105 |
| Dysgeusia | Nervous system disorders | 0 of 65 | 0 of 70 | 0 of 104 | 1 of 105 |
| Pruritus | Skin and subcutaneous tissue disorders | 0 of 65 | 0 of 70 | 0 of 104 | 1 of 105 |
| Nausea | Gastrointestinal disorders | 0 of 65 | 0 of 70 | 1 of 104 | 0 of 105 |
The registry reports serious adverse events by listed study group. The recorded serious adverse event count is 0 among 65 at risk in the MultiHance 0.1 mmol/kg group, 0 among 70 at risk in the Dotarem 0.1 mmol/kg group, 0 among 104 at risk in the MultiHance 0.05 mmol/kg group, and 0 among 105 at risk in the Dotarem 0.1 mmol/kg group. These entries describe the recorded groups and should not be converted into broader conclusions about comparative safety.
For other adverse events, the registry records 1 among 65 at risk for MultiHance 0.1 mmol/kg, 2 among 70 at risk for Dotarem 0.1 mmol/kg, 3 among 104 at risk for MultiHance 0.05 mmol/kg, and 7 among 105 at risk for Dotarem 0.1 mmol/kg. The record does not provide event terms for these entries, their severity beyond the serious/non-serious distinction, or a statistical comparison. The listed groups occur in a crossover study, and the registry does not explain whether the group counts represent unique participants or how repeated exposure was handled in these safety summaries.
In general, adverse-event counts are descriptive and depend on how events were defined, collected, and attributed. A zero count in a listed group means no serious event was recorded for that group in the registry entry; it does not establish absence of risk. Death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry establishes that a Phase IV randomized, triple-masked crossover study compared MultiHance at 0.1 mmol/kg and 0.05 mmol/kg with Dotarem at 0.1 mmol/kg in brain MRI. It identifies a reader-rated primary endpoint and states that 3 blinded readers assessed paired exams. The primary question was whether readers preferred one image set or considered the exams equal.
The posted registry information does not report the primary outcome category counts, a treatment contrast, uncertainty intervals, or a statistical test. It therefore does not establish the direction or size of reader preference, whether readers agreed, or how precisely any preference was estimated. The stated aim to show superiority is not itself a result. No claim that either agent was preferred, or that the agents were equivalent, can be drawn from the information reported in the registry.
The registry includes 179 participants in the enrollment record and describes 159 patients with post-dose exams for both MultiHance doses and Dotarem. Those figures do not by themselves show how many contributed to each reader’s analysis. Technically inadequate images could be excluded for an individual reader, and the analyzed numbers differed slightly across readers and endpoints. The per-protocol population also had additional requirements.
The adverse-event entries report zero serious adverse events in each listed group and record non-serious event counts. These entries do not constitute a comparative safety analysis, and death counts are not reported. The registry also lists multiple outcomes and analyses but does not state a multiplicity strategy. Thus the record supports a description of the study design and recorded safety counts, not a complete assessment of efficacy, precision, or comparative safety.
13. Why This Trial Matters Statistically
This trial is statistically notable for its crossover structure and reader-rated imaging endpoint. A crossover design makes the pairing of observations central: each participant’s image sets are linked, and a valid comparison generally needs to reflect that dependence. The registry identifies different treatment orders, but does not report how the paired data, sequence, or possible period effects were handled. That distinction matters because a design description is not a substitute for a statistical model.
The endpoint also involves judgment by 3 blinded readers. In general, multiple readers can strengthen an imaging assessment by incorporating more than one interpretation, but their ratings may differ. Reader-specific results and a stated approach to combining readers are important to understand whether a preference is consistent or depends on particular assessments. Those results and methods are not reported in the registry record.
There is a substantial distinction between the stated superiority aim and the available outcome information. The registry identifies the preference categories but does not report their counts or a comparative estimate. Without those results, the magnitude and precision of the primary comparison cannot be assessed. The study’s listed 7 outcome measures and 42 analyses also make the analysis plan relevant to interpretation, yet multiplicity handling is not reported.
The record is still informative about the structure of the research question: a comparison of two MultiHance doses against Dotarem at the same stated dose, in paired brain MRI exams, assessed by blinded readers. It also identifies the per-protocol population and the possibility of reader-specific image exclusions. These details help define what an eventual analysis would need to address, while leaving the actual primary result unresolved in the registry record.
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 most important limitation of the registry record for interpreting this trial is that it does not report the primary endpoint results. The preference categories are defined, but counts by category, reader-specific results, estimates of comparative effect, uncertainty intervals, and p-values are not reported in the registry record. The study’s stated superiority aim therefore cannot be evaluated using the posted outcome information.
Although the primary outcome description identifies 3 blinded readers, the registry does not describe the statistical method for combining their assessments or report agreement among them. It notes that reader-specific denominators differed slightly because technically inadequate image sets were excluded. The exact denominators and exclusion counts are not reported. The per-protocol criteria are stated, but participant flow into and out of that population is not fully described.
The crossover sequences are listed, but the registry does not report sequence allocation counts, washout details, or analyses of period and carryover effects. The timeframe of image sets obtained within 2 to 14 days does not by itself establish the washout procedure. Details of random sequence generation and the specific roles covered by triple masking are also not reported.
The registry records 7 outcome measures and 42 analyses without reporting a multiplicity approach. The analysis plan, model specification, and handling of missing data are not reported. The planning illustrations use the observed effect and stated assumptions, but the trial’s own sample-size justification is not reported. Finally, the adverse-event entries do not include event terms for the non-serious counts or a comparative safety analysis, and death counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Crossover Comparison of MultiHance and Dotarem — NCT02070380.
- Registry record last updated 2017-01-10; status last verified 2016-11.
- Results first posted 2017-01-10.
- 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.
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18. Record Summary
The registry record describes NCT02070380, “Crossover Comparison of MultiHance and Dotarem,” as a Phase IV randomized, triple-masked, multi-center crossover study. It records enrollment of 179 participants, a completed status, a start of 2014-02, and primary completion of 2015-03.
The study compared MultiHance at 0.1 mmol/kg and 0.05 mmol/kg with Dotarem at 0.1 mmol/kg in brain MRI. The primary endpoint was global diagnostic preference between paired exams, assessed by 3 blinded readers. The endpoint description concerns 159 patients with post-dose exams for both MultiHance doses and Dotarem; technically inadequate images could be excluded for a given reader. The per-protocol population required completed exams, global paired image data, and no major protocol violations.
The registry lists 7 outcome measures and 42 analyses. It records no serious adverse events in the listed groups and reports other adverse event counts, but does not report the primary preference results, a statistical comparison, or death counts. Multiplicity handling, missing-data methods, and the trial’s sample-size justification are not reported in the registry record.