Evaluation of Safety and Efficacy of Lumason in Pediatric Echocardiography: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety and Efficacy of Lumason in Pediatric Echocardiography (NCT02282163), a na phase 3 study. The primary outcome is Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores.

2. Clinical Question

3. Trial Design

This was a Phase 3, multicenter, single-group clinical evaluation of Lumason in pediatric echocardiography. The official title describes an evaluation of safety and efficacy as a contrast agent. The trial record lists Heart Disease as the condition and Bracco Diagnostics, Inc as the sponsor. Enrollment is listed as 13. The study started in 2015-10, had a primary completion date of 2018-05-31, and is recorded as terminated. The reason for termination is not reported in the registry record.

The study did not have randomized allocation or a separate comparator arm: allocation is recorded as not applicable, masking as none, and the model as single group. The Lumason arm description says all patients received one 0.03 mL/kg bolus during echocardiography. In the endpoint, the comparison is between images obtained with unenhanced ultrasound and contrast-enhanced ultrasound, rather than between Lumason and an independently assigned control group. This distinction matters: the modality contrast is useful for describing the paired imaging assessment, but it does not create the same design protections as random assignment to treatment groups.

The brief summary describes subjects aged 9 to 17 years with suboptimal left ventricular endocardial border delineation on non-contrast two-dimensional echocardiography. It also states that the imaging modalities used in pediatric subjects represented those utilized in routine clinical practice in adults. The record does not provide further details about site procedures, eligibility criteria, or how readers were assigned images. Those details are not reported in the registry record.

The listed primary completion date refers to completion of the primary outcome period; it should not be confused with evidence that the registry includes numerical outcome findings. Although the record defines primary and secondary outcomes, it lists zero analyses. The status is terminated, but that status alone does not explain why the trial ended or what conclusions the sponsor drew.

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: The study was terminated early due to challenges with enrollment. At the time of termination, 13 subjects were enrolled and 12 subjects were dosed with Lumason, thus the efficacy analysis was considered as exploratory and p-values are not included in the Results section. PK assessment was not performed due to enrollment difficulties.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who received IP and had data available for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS) were included in ITD population.

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 Change From Baseline in Total Left Ventricular Endocardial Border Delineation (LV EBD) Scores, measured over Immediately post dose-Day 1.

The primary endpoint is change from baseline in total left ventricular endocardial border delineation (LV EBD) score, assessed immediately post dose on Day 1. The measure describes how clearly the boundary of the left ventricle can be delineated in echocardiographic images. It is based on ratings for 17 segments drawn from the apical 4-chamber, apical 2-chamber, and apical long (3-chamber) views, following the American Society of Echocardiography guidelines.

Each segment receives a score of 0 for inadequate, 1 for sufficient, or 2 for good delineation. The segment scores are summed into a total score that can range from 0 to 34. The record says that the endpoint is reported for each of three readers, for both unenhanced ultrasound (UEUS) and contrast-enhanced ultrasound (CEUS). It defines change from baseline as the difference between UEUS and CEUS total scores, without specifying a subtraction order in the description.

This endpoint is used to assess image delineation, not a clinical outcome such as symptoms or a health event. A score can indicate image quality under the stated rating system, but it does not by itself establish the accuracy of a diagnosis or a change in a patient’s health. The registry record identifies the mean as the summary measure and a 95% confidence interval as the dispersion measure. It does not report the numerical endpoint findings, so the observed difference and its precision cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous score summarized by a mean. A mean describes the average score across the included observations; it does not show how much individual scores vary. The registry record identifies a 95% confidence interval as the dispersion measure. In general, a confidence interval communicates uncertainty in an estimated quantity under the assumptions of the analysis. It is different from the range of individual participant scores. Here, the record defines the intended form of the summary but contains no numerical mean or interval values.

What does the score represent?

The endpoint combines ratings of left ventricular endocardial border delineation across 17 specified segments. Each segment is rated as inadequate, sufficient, or good, with scores of 0, 1, or 2 respectively. Summing those ratings produces a total that can range from 0 to 34. The method gives a structured way to convert image assessments into a numerical summary. As with any rating scale, interpretation depends on how consistently readers apply the scoring criteria. The record identifies three readers but does not report reader-specific results, agreement statistics, or procedures for resolving disagreements.

The total score is a bounded score assembled from ordered categories. The registry describes it as a mean-based continuous outcome, but that description does not itself show the score distribution or whether a mean captures all relevant features of the observations. Without the posted scores or distributions, it is not possible to assess how concentrated, dispersed, or skewed the measurements were. No alternative summary measure is reported in the registry record.

How should the modality comparison be understood?

The primary outcome compares UEUS and CEUS scores. It is a within-study modality comparison, not a comparison of separate randomized arms. In general, paired measurements can account for the fact that two observations come from the same participant, because the analysis can use their relationship. The registry record does not describe the exact statistical model or calculation used for the comparison, beyond defining change as the difference between UEUS and CEUS total scores and identifying the mean and 95% confidence interval as summary measures. It would be inappropriate to infer an unreported model, adjustment, or test.

The record presents scores for each of three readers. Reader-level estimates can help show whether the pattern is consistent across image assessors, but the numerical estimates are not reported. It is also not stated whether the reader results were combined, analyzed separately, or treated in some other way. The registry record does not report a reader training or blinding procedure.

What does a confidence interval add?

As a general statistical concept, a confidence interval places an estimate in the context of sampling uncertainty. A point estimate alone gives a central value; an interval also conveys how precisely that value has been estimated under the chosen method. A confidence interval is not a substitute for judging the design, measurement quality, or relevance of the endpoint. Nor does an interval alone establish whether an effect is important. The numerical intervals and any threshold for interpreting a meaningful score change are not reported in the registry record.

The primary endpoint’s specified timeframe is immediately post dose-Day 1. This makes the measure an immediate imaging assessment in the recorded study, not an estimate of longer-term change. The registry record does not identify another primary-outcome follow-up time or state whether the score change was assessed repeatedly.

What can planning calculations say?

General sample-size calculations ask how many participants per arm might be needed under chosen assumptions to detect a specified effect with a chosen statistical procedure. They are planning illustrations, not descriptions of what happened in a completed study. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions do not match the recorded single-group study as a description of its actual allocation, which has no separate randomized arms.

The record does not report the observed primary effect needed to interpret such planning illustrations, nor does it report a statistical plan explaining how the planning assumptions relate to this study. Any planning value should therefore be read as a hypothetical illustration based on its stated assumptions, not as observed power, a trial result, or evidence that the study was designed around a particular effect. The registry record does not report a sample-size justification.

What statistical information is absent?

The registry record lists zero analyses and contains no numerical primary-outcome results or test statistics. It does not report the analysis model, handling of repeated reader assessments, a missing-data method, an adjustment for multiple comparisons, or interim analyses. These absences limit reproducibility and the ability to judge the precision and robustness of the endpoint findings. General statistical methods cannot fill in those trial-specific details; they remain not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and identifies change from baseline in total LV EBD score as the primary outcome. It lists number of participants with adverse events as a secondary outcome. It does not provide the full numerical results for the primary endpoint, and it does not report a multiplicity strategy. A multiplicity strategy describes how statistical inference is handled when several outcomes, time points, readers, or comparisons are considered. Without a reported strategy, it is not possible to say whether any adjustment was planned or applied. The record lists zero analyses, so no inferential approach can be reconstructed from the registry entry.

The primary-outcome population is defined as subjects who received the investigational product and had available data for both UEUS and CEUS. This definition makes availability of paired modality data part of inclusion in that outcome population. The record does not report the number included under that definition, the number with missing imaging data, or reasons for any missing data. It also does not describe imputation, exclusion, or sensitivity analyses. Those methods are not reported in the registry record.

Enrollment is recorded as 13, while the safety summaries give an at-risk denominator of 12. The record does not explain the relationship between enrollment and the safety population, and the primary-outcome population is separately defined by data availability. These figures should not be merged or treated as if they describe identical analysis populations. The registry record does not report an intention-to-treat analysis or a per-protocol analysis by name, nor does it give further population definitions beyond the primary outcome description.

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 non-serious adverse event terms

The registry’s safety summary lists 12 participants at risk for serious adverse events and 12 at risk for other adverse events. It records zero participants affected by serious adverse events, five affected by other adverse events, and zero deaths. These are counts with their listed denominators; they should not be converted into percentages or treated as a complete description of event severity, timing, or causality. The registry lists no top serious-event terms.

The summary does not provide event-level descriptions, the number of events per participant, timing, duration, outcome, or an assessment of whether an event was considered related to Lumason. It also does not explain why the safety denominator differs from the enrollment entry. The listed counts describe only the registry’s reported safety categories and should not be read as a full account of safety findings. The record does not report further detail on the other adverse events or the criteria used for classifying events.

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

The record documents a study designed to assess safety and imaging-related efficacy of Lumason in pediatric echocardiography. Its primary outcome is a reader-rated score of left ventricular endocardial border delineation, comparing unenhanced and contrast-enhanced ultrasound. The endpoint definition, scoring scale, assessment views, readers, and timeframe are described. The registry also reports safety counts for serious adverse events, other adverse events, and deaths.

What the record does not establish is the numerical size or precision of the primary endpoint difference. Although it defines the mean and 95% confidence interval as the intended summary, it does not provide those numerical results. Thus, the posted registry record cannot show whether scores differed, how large any difference was, or how consistent the estimates were across readers. This absence should not be interpreted as a finding of no difference.

The design also limits what can be inferred. There was one study group and no separate randomized control group. The endpoint’s comparison of imaging modalities is not a randomized comparison of treatment groups, and masking is listed as none. The record therefore cannot support a causal claim based on randomized assignment, and its reader-based endpoint should not be mistaken for a direct clinical outcome.

The safety counts are similarly bounded by what is recorded. The summary reports zero participants with serious adverse events, five with other adverse events, and zero deaths among the listed safety group. It does not supply the event detail needed to characterize timing, relatedness, or clinical course. The study status is terminated, but the reason is not reported in the registry record. Taken together, the record gives a useful description of the study design, endpoint, and selected safety counts, while leaving the primary numerical findings and several analytic details unavailable.

13. Why This Trial Matters Statistically

This trial is statistically notable because its main comparison is embedded in a single-group imaging study rather than a randomized parallel-group design. UEUS and CEUS are the two modalities used to assess the endpoint, and the outcome is defined as the difference between their total LV EBD scores. Understanding that structure prevents a common interpretation error: a within-study modality contrast is not the same estimand as the effect of assigning participants to one treatment group rather than another.

The endpoint also illustrates the distinction between a measurement process and a patient outcome. The total score turns ordered segment ratings into a numerical measure of image delineation. Three readers are named in the outcome description, making reader-level assessment part of the endpoint framework. Yet the registry record does not report reader-specific values, agreement, or the method for combining assessments. Those details matter when an outcome depends on image interpretation.

The record’s missing numerical primary results are consequential. A defined endpoint and specified confidence-interval format do not provide the estimate itself. Without the score changes and intervals, readers cannot evaluate magnitude or precision. This is a statistical limitation of the registry entry, not proof that the study found no difference.

Finally, the record distinguishes enrollment, endpoint eligibility, and safety summaries. The primary population requires both modality measurements, while the safety summaries use their own at-risk denominator. Keeping these populations separate is essential when interpreting reported counts or estimates. The study is therefore a useful example of why design, estimand, analysis population, and result reporting all need to be considered together.

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 direct limitation of the registry record is that it does not report numerical results for the primary endpoint. The endpoint definition includes the score scale, modalities, readers, summary measure, confidence-interval type, and timeframe, but the actual mean scores, changes, and confidence intervals are absent. Consequently, neither magnitude nor precision can be evaluated.

The design is single group, with allocation listed as not applicable and masking as none. There is no separate randomized comparator. The modality comparison may describe paired image assessments, but the record does not specify the statistical calculation in enough detail to assess how pairing or reader-level results were handled. It also does not report reader agreement or blinding procedures.

The primary-outcome population is defined by receipt of the investigational product and availability of data from both imaging modalities. The number meeting that definition is not reported. Enrollment is listed as 13, while the safety summary uses 12 at risk; the registry does not explain the difference. Missing-data counts, reasons, and methods are not reported.

The status is terminated, but the reason is not reported in the registry record. The registry lists three outcome measures and zero analyses, and does not describe a multiplicity approach, interim analyses, a statistical plan, or a sample-size justification. Safety reporting is also limited: the summary does not give event-level terms for serious events, and no top serious-event terms are listed. These gaps do not establish that additional analyses or details did not exist; they mean they are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Safety and Efficacy of Lumason in Pediatric Echocardiography — NCT02282163.
• Registry record last updated 2020-07-13; status last verified 2020-06.
• Results first posted 2020-06-16.
• 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

NCT02282163 is a multicenter Phase 3, single-group study of Lumason in pediatric echocardiography. It enrolled 13 and is recorded as terminated. Participants received a single 0.03 mL/kg bolus during echocardiography. The primary endpoint was change in total LV EBD score between UEUS and CEUS immediately post dose-Day 1, assessed by three readers and defined on a scale from 0 to 34. Numerical primary-outcome results are not reported in the registry record. The safety summary lists 12 at risk for serious and other adverse events, with zero participants affected by serious adverse events, five affected by other adverse events, and zero deaths. The reason for termination and several analysis details are not reported.