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 An Efficacy and Safety Study of Sonazoid™ and SonoVue® in Participants With Focal Liver Lesions, Undergoing Pre- and Post-Contrast Ultrasound Imaging (NCT03335566), a randomized phase 3 study. The primary outcome is Percentage of Participants With Accuracy Improvement in Post-Contrast Versus Pre-Contrast Ultrasound (US) Examination for Diagnosis of the Target Lesion as Malignant or Benign Against the Reference Diagnosis (RD)/Standard of Truth.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03335566 |
| Phase | Phase 3 |
| Condition | Liver Lesions |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 424 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GE Healthcare |
| Results posted | Yes |
2. Clinical Question
Population
Participants had focal liver lesions and underwent ultrasound examinations before and after contrast administration. The efficacy population included participants who received either study agent, had pre-contrast and post-contrast images recorded, and had a reference-standard contrast-enhanced computed tomography examination, contrast-enhanced magnetic resonance imaging examination, or biopsy. The registry record says the primary analysis used this efficacy population; the number analysed for a category was the number with available data for that category.
Intervention
One group received a single intravenous bolus injection of Sonazoid™ at 0.12 microliter of microbubbles per kilogram of body weight. The contrast ultrasound examinations assessed lesion diagnosis and imaging features before and after administration. The primary endpoint concerned whether diagnostic accuracy improved after contrast administration.
Comparator
The randomized parallel-group comparison was between Sonazoid™ and SonoVue®. The SonoVue® group received a single intravenous bolus injection of 2.4 milliliter. The trial was unmasked, so masking was not used. The registry record does not describe additional measures to conceal the assigned agent from participants or study personnel.
Primary question
The primary endpoint asks about the percentage of participants whose post-contrast ultrasound diagnosis of the target lesion as malignant or benign was more accurate than their pre-contrast diagnosis, judged against a reference diagnosis or standard of truth. The registry record does not report the numerical result for either group or a between-group estimate. It therefore does not establish from the posted primary endpoint whether accuracy improvement differed between the agents.
3. Trial Design
This was a Phase 3, multicentre, randomized, comparative study with a parallel-group design. The two interventions were Sonazoid™ and SonoVue®, and the registry record lists masking as none. The study is marked completed, with enrollment of 424 participants. The registry dates are 2014-05-11 for study start and 2015-04-09 for primary completion.
Participants with focal liver lesions underwent pre-contrast and post-contrast ultrasound imaging. The Sonazoid™ arm used a single intravenous bolus dose of 0.12 microliter of microbubbles per kilogram of body weight; the SonoVue® arm used a single intravenous bolus dose of 2.4 milliliter. The study purpose was comparative: to assess diagnostic findings and other imaging characteristics after contrast administration relative to pre-contrast imaging. The registry description also identifies lesion detection, diagnostic confidence, specific lesion diagnosis, and delineation of lesion-related blood vessels and the whole liver among the areas of interest.
The primary endpoint focused on accuracy improvement for classifying the target lesion as malignant or benign, using a reference diagnosis or standard of truth. The registry says assessments were done by three blinded readers, even though the study-level masking field is none. These are distinct details: the record describes blinded readers for assessment, while the overall trial is listed as unmasked. The practical blinding procedures and how reader assessments were combined are not reported in the registry record.
The primary analysis population was defined by receipt of either agent, availability of pre-contrast and post-contrast images, and availability of a reference-standard contrast-enhanced computed tomography examination, contrast-enhanced magnetic resonance imaging examination, or biopsy. The actual number analysed for the primary endpoint is not reported in the registry record. The registry lists four outcome measures, but a numerical primary endpoint result and a formal treatment comparison are not reported.
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: Participants were randomised in 1:1 ratio to receive either Sonazoid™ or SonoVue®.
Overall Study
| Stage | Sonazoid™ | SonoVue® |
|---|---|---|
| STARTED | 218 | 206 |
| COMPLETED | 214 | 203 |
| NOT COMPLETED | 4 | 3 |
Reasons for not completing this period:
| Reason | Sonazoid™ | SonoVue® |
|---|---|---|
| Adverse Event | 0 | 1 |
| Lost to Follow-up | 1 | 0 |
| Technical Problems | 1 | 0 |
| Protocol Violation | 1 | 0 |
| Other than specified above | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on efficacy population. Here, number analysed=participants with available data for specified category.
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: Analysis was performed on safety analysis set that included all enrolled participants who received either Sonazoid™ or SonoVue.
| Characteristic | Unit | Sonazoid™ | SonoVue® | Total |
|---|---|---|---|---|
| Participants analysed | 218 | 206 | 424 | |
| Age, Continuous | years | 54.5 (SD 12.61) | 52.2 (SD 13.77) | 53.4 (SD 13.22) |
| Sex: Female, Male: Female | Participants | 81 | 81 | 162 |
| Sex: Female, Male: Male | Participants | 137 | 125 | 262 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 218 | 206 | 424 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Accuracy Improvement in Post-Contrast Versus Pre-Contrast Ultrasound (US) Examination for Diagnosis of the Target Lesion as Malignant or Benign Against the Reference Diagnosis (RD)/Standard of Truth, measured over Pre-administration up to 15 minutes post-administration.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants whose diagnosis of the target lesion improved in accuracy from the pre-contrast ultrasound examination to the post-contrast examination. Accuracy was judged against a reference diagnosis or standard of truth, and the target classification was malignant versus benign. The registry defines the percentage as the number of participants with an improved diagnosis divided by the total number of participants, multiplied by 100. Assessments were made by three blinded readers during the timeframe from pre-administration up to 15 minutes post-administration.
This endpoint is intended to capture a change in diagnostic correctness, rather than simply a change in reader confidence or image appearance. Comparing the diagnoses against a reference standard makes it possible to distinguish an accurate change from a change that does not match the reference. A percentage expresses how common such improvement was within the analysed population, but its interpretation depends on the denominator, completeness of reference-standard data, and the rule used to combine reader assessments. Those details beyond the stated population and reader count are not reported in the registry record.
The registry record does not report the observed percentages, uncertainty estimates, or a statistical comparison between Sonazoid™ and SonoVue®. It also does not state whether unchanged or less accurate diagnoses were summarized separately within the primary outcome. Without those numerical results and analysis details, the endpoint definition can be described, but the magnitude and precision of any difference cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the design and definition of the primary endpoint, but it does not report the primary endpoint values. No numerical percentage of participants with accuracy improvement is available for either Sonazoid™ or SonoVue® in the registry record. A between-group estimate, confidence interval, and p-value are also not reported in the registry record. Accordingly, the posted information does not show the size, direction, or precision of a comparative effect on the primary endpoint.
The endpoint concerns accuracy improvement from pre-contrast to post-contrast assessment relative to a reference diagnosis. It is not a direct count of all correct diagnoses, and the definition alone does not indicate how many participants improved, remained unchanged, or had a less accurate diagnosis. Those distinct outcome patterns should not be inferred from the endpoint title. The registry record states that the percentage was calculated from participants with improved diagnoses and the total number of participants, but the observed numerator and denominator are not reported.
Interpretation also depends on the analysis population. The efficacy population required images from both examination conditions and a reference standard from contrast-enhanced computed tomography, contrast-enhanced magnetic resonance imaging, or biopsy. Participants lacking one of these elements would not meet that stated definition. The number who met the criteria, and whether missing information differed between randomized groups, are not reported in the registry record. These omissions limit assessment of how representative the analysed participants were of all enrolled participants.
Three blinded readers assessed the endpoint. Reader blinding can help reduce bias in image interpretation, but the registry record does not describe how reader-level diagnoses were combined, whether readers assessed images independently, or how disagreements were handled. The study itself is listed as unmasked. Therefore, the reader-blinding detail should not be taken as evidence that every aspect of study conduct or assessment was masked.
The random allocation and parallel-group structure support a comparative design, but they do not substitute for the outcome results or analysis plan. Allocation procedures, planned statistical methods, adjustment factors, and handling of multiplicity are not reported in the registry record. No treatment conclusion should be drawn from the design description or endpoint definition alone. The posted information permits a description of what the trial set out to compare, not an estimate of the comparative diagnostic effect.
The adverse-event figures report zero serious adverse events and zero other adverse events in each arm, with zero deaths recorded. These are the posted counts for the listed categories and at-risk groups; they should be read as registry entries, not as proof that no adverse experiences occurred outside the reported categories or observation period. The detailed safety definitions, collection procedures, and follow-up duration are not reported in the registry record.
9. Statistical Methods Explained
The primary endpoint is a binary participant-level event summarized as a percentage: whether diagnostic accuracy improved between pre-contrast and post-contrast ultrasound. A binary endpoint places each participant into a category according to whether the defined event occurred. The registry describes the event as an improved diagnosis against the reference diagnosis or standard of truth. The registry record does not report the resulting event counts or percentages, so no estimate of the event frequency or difference between groups can be interpreted.
What a percentage describes
A percentage uses a numerator and a denominator. Here, the numerator is the number of participants whose diagnosis improved, and the denominator is the total number of participants in the relevant analysis. The registry states that the efficacy population included participants with both sets of ultrasound images and an available reference standard. It further notes that the number analysed was the number with available data for the specified category. The actual category-specific denominators are not reported in the registry record. A percentage without its denominator can be difficult to assess, because the same percentage may have different precision depending on how many observations contributed.
Why compare pre-contrast and post-contrast findings
The endpoint is framed as a change in diagnostic accuracy within the imaging sequence. Each participant’s pre-contrast diagnosis is compared with the post-contrast diagnosis, and accuracy is assessed against a reference. This approach asks whether diagnostic classification improved after contrast administration, rather than asking only whether readers gave a particular diagnosis after the procedure. In general, a change is not automatically an improvement: the comparison with the reference standard is what defines whether the change is more accurate. The registry record does not give the counts for unchanged or less accurate diagnoses, so these outcomes cannot be described from the posted primary result.
Reader assessment and reference standards
The registry says three blinded readers assessed the primary endpoint. Blinding readers to treatment assignment or other information can reduce the risk that expectations influence image interpretation; that is a general methodological rationale, not a claim about the exact blinding procedures used in this trial. The record lists the overall trial masking as none and does not explain how reader blinding was implemented. It also does not report whether reader assessments were combined by consensus, averaged, adjudicated, or analysed separately. The reference standard could be contrast-enhanced computed tomography, contrast-enhanced magnetic resonance imaging, or biopsy. Differences among reference procedures may matter when interpreting a diagnostic endpoint, but the registry record does not provide details on their use or consistency.
Uncertainty and treatment comparisons
A confidence interval is a statistical summary of uncertainty around an estimate. In general, it helps readers judge which effect sizes are compatible with the data under the analysis assumptions. A p-value, when reported, summarizes how incompatible the data are with a specified null hypothesis under a statistical model; it does not measure clinical importance. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. The statistical model, test, confidence level, and contrast used for the primary comparison are also not reported. As a result, the precision and statistical evidence for a difference between arms cannot be evaluated.
Randomization is intended to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. That design feature supports causal interpretation when allocation is implemented appropriately and follow-up and analysis preserve the benefits of randomization. The registry identifies the study as randomized but does not report the sequence-generation or allocation-concealment procedures. It also does not report whether the primary analysis followed assigned groups or how deviations from assignment were handled. These are relevant implementation details, not grounds to presume a specific method.
Planning assumptions and over-dispersion
Sample-size planning is distinct from observed results. In general, a planning calculation asks how much information may be needed to detect an assumed effect under specified model and error-rate assumptions. Such an illustration is not observed power and does not show that a study did or did not find an effect. The registry record does not report the trial’s own sample-size justification, target effect, or planned power. No planning result should be read as a trial outcome.
Over-dispersion is a general concern when observed variation exceeds what a statistical model assumes. For a binary percentage, the particular implications depend on the model, clustering, repeated assessments, and the unit of analysis. This study involved reader assessments, but the registry record does not specify the analysis structure or report a model for those assessments. It is therefore not possible to determine whether over-dispersion was relevant or how it was handled. The analysis plan, interim analyses, and adjustment methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and identifies the accuracy-improvement endpoint for malignant versus benign classification as primary. It also lists outcomes concerning lesion detection, diagnostic confidence, and accuracy improvement for lesion-specific diagnoses. When a study assesses several outcomes, time points, readers, or categories, the chance of obtaining an apparently notable result among many comparisons may increase. Statistical approaches can account for this multiplicity, but the registry record does not report a multiplicity strategy, a hierarchy of tests, or which outcomes were included in any confirmatory testing procedure. No analysis results are reported for the primary endpoint, and the registry lists zero analyses.
The efficacy population required pre-contrast and post-contrast images and a reference standard. The registry describes the number analysed for a category as the number with available data for that category. This indicates that availability of category-specific data mattered to analysis, but it does not explain how missing images, missing reference diagnoses, or other unavailable data were handled. The number excluded for missing information, the reasons for missingness, and any imputation or sensitivity analyses are not reported in the registry record.
Randomization can support a fair comparison, but exclusions after randomization can affect comparability if they differ across arms or relate to outcomes. The registry record does not provide the participant flow or the number analysed for the primary endpoint by arm. It also does not specify an intention-to-treat analysis or another analysis population beyond the stated efficacy definition. The impact of missing data and exclusions therefore cannot be assessed from the posted information.
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 |
|---|---|---|---|
| Sonazoid™ | 0 | 218 | 0.0% |
| SonoVue® | 0 | 206 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sonazoid™ | 0 of 218 |
| SonoVue® | 0 of 206 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sonazoid™ | 0 of 218 |
| SonoVue® | 0 of 206 |
The registry lists 218 participants at risk for serious adverse events in the Sonazoid™ group and 206 in the SonoVue® group. It reports zero participants affected by serious adverse events in each group. For other adverse events, the at-risk counts are also 218 and 206, with zero affected in either group. Deaths are listed as zero in both groups. No top serious adverse-event terms are listed.
These figures are counts for the categories recorded in the registry. A zero count means no affected participants are reported in that particular category in the posted record; it does not establish that the agents have no risks. The registry record does not report the adverse-event definitions, event-collection methods, observation period, severity criteria, or detailed safety analyses. It also does not provide event-level descriptions for the other adverse-event category. The at-risk counts should not be confused with the efficacy analysis denominator, which is defined by image and reference-standard availability.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized comparison of Sonazoid™ and SonoVue® in participants with focal liver lesions who underwent ultrasound imaging before and after contrast administration. Its primary endpoint was designed to measure the percentage of participants whose diagnosis of the target lesion as malignant or benign improved in accuracy relative to a reference diagnosis or standard of truth. The record also identifies three blinded readers and defines the efficacy population by receipt of study agent, image availability, and reference-standard availability.
Those design and endpoint details do not establish what the trial found. The primary endpoint percentages, participant counts, uncertainty estimates, and statistical comparison are not reported in the registry record. There is therefore no basis in the posted primary outcome information for stating which arm had a higher accuracy-improvement rate, how large any difference was, or whether the estimate was precise. The endpoint definition should not be mistaken for a result.
The registry’s safety entries report zero serious adverse events, zero other adverse events, and zero deaths in both arms. These entries describe the listed safety categories and at-risk groups. They do not establish the absence of all adverse experiences, and the registry record does not give the duration or detail needed to evaluate the full safety profile.
More broadly, the record does not report the statistical analysis plan, the treatment of missing data, the multiplicity strategy, or the sample-size justification. Such information affects how strongly a result can be interpreted, even when numerical outcomes are available. In this case, because the primary numerical results themselves are not reported, the conclusions must remain limited to the trial’s design, intended endpoint, analysis-population definition, and posted safety counts. No claim about comparative efficacy follows from those descriptions alone.
13. Why This Trial Matters Statistically
This trial raises statistical questions that are central to diagnostic-imaging studies. The endpoint is not simply whether an image changed a reader’s opinion; it is whether diagnosis improved in accuracy against a reference standard. That distinction makes the outcome clinically interpretable as a diagnostic classification measure, while also making it dependent on the reference procedure and the rules used to define improvement.
The pre-contrast and post-contrast structure allows the endpoint to focus on change within participants, while randomized allocation supports a comparison between the two contrast-agent groups. These design features address different questions: within-participant change concerns whether the diagnostic assessment improved after contrast, whereas the randomized comparison concerns whether the measured improvement differed between agents. A clear statistical analysis must connect the endpoint definition to the intended comparison and account for the data structure, including reader assessments. The registry record does not report the analysis details needed to see how this was done.
The efficacy population also highlights the role of data availability in diagnostic research. An interpretable accuracy assessment requires both the imaging observations and a reference diagnosis. If either is unavailable, the participant may not contribute to the defined endpoint. Knowing the numbers and reasons for exclusions is important for understanding whether the analysed group reflects the randomized participants and whether missing information could bias the comparison. Those details are not reported in the registry record.
Finally, the contrast between a detailed endpoint definition and absent numerical outcome results illustrates why design registration and outcome reporting serve different purposes. A registry description can clarify what was planned or measured, but it cannot replace estimates and uncertainty measures. For this trial, the endpoint and design are described; the comparative result is not reported.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for statistical interpretation is that numerical primary endpoint results are not reported in the registry record. The percentages, denominators, between-group estimate, confidence interval, and p-value are unavailable. The size and precision of any difference therefore cannot be evaluated. The record also does not report numerical results for the other listed outcomes.
The analysis population is defined, but its size is not stated. The registry record does not give the number of randomized participants included in the efficacy analysis by arm, the number with missing images or reference standards, or reasons for unavailable data. It is consequently not possible to assess whether exclusions affected the groups differently or how representative the analysed population was.
Important analytical details are not reported in the registry record. These include the statistical model or test, the method for combining the assessments of the three blinded readers, treatment of reader disagreement, handling of missing data, multiplicity control, and interim analyses. The record also does not state the trial’s sample-size justification. The overall study is listed as unmasked, while the primary assessments are described as having been done by blinded readers; implementation details explaining that distinction are not reported.
The safety entries are limited to the posted counts for serious adverse events, other adverse events, and deaths. Definitions, observation duration, collection procedures, and event-level detail are not reported in the registry record. These limitations mean the listed zero counts should be interpreted narrowly rather than as a complete characterization of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Efficacy and Safety Study of Sonazoid™ and SonoVue® in Participants With Focal Liver Lesions, Undergoing Pre- and Post-Contrast Ultrasound Imaging — NCT03335566.
- Registry record last updated 2018-10-31; status last verified 2018-10.
- Results first posted 2018-08-27.
- 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.
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18. Record Summary
NCT03335566 is a completed, randomized, unmasked, parallel-group Phase 3 comparative study sponsored by GE Healthcare. The registry lists enrollment of 424 participants and a multicentre study of Sonazoid™ and SonoVue® in participants with focal liver lesions. Study start is listed as 2014-05-11 and primary completion as 2015-04-09.
The primary endpoint was the percentage of participants whose post-contrast ultrasound diagnosis of the target lesion as malignant or benign improved in accuracy relative to a reference diagnosis or standard of truth. The efficacy population required receipt of study agent, recorded pre-contrast and post-contrast images, and an available reference-standard examination or biopsy. Assessments were done by three blinded readers.
The registry record does not report numerical primary outcome results or a statistical comparison. It reports zero serious adverse events, zero other adverse events, and zero deaths in both groups.