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 Contrast Enhanced Ultrasound in COVID-19 (NCT04640038), a na phase 3 study. The primary outcome is Estimate the Proportion of Patients With Normal Perfusion Versus Area(s) of Hypoperfusion in Heart, Kidneys and/or Brain.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04640038 |
| Phase | Phase 3 |
| Condition | Covid19, Multisystem Inflammatory Syndrome in Children (MIS-C) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's Hospital of Philadelphia |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns pediatric patients with confirmed or probable COVID-19. The registry lists COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C) as conditions. Enrollment was 4. The record does not report further eligibility details in the information available for the primary outcome.
Intervention
The study used contrast-enhanced ultrasonography (CEUS), with intravenous administration of sulfur hexafluoride lipid-type A microspheres before imaging. The intended assessment was microvascular perfusion in the heart, kidneys and/or brain. The record describes CEUS as a bedside imaging approach; it does not provide a comparison with another imaging method.
Comparator
There was no separate comparator group. The registered model is single-group, and allocation is listed as not applicable. The intervention group therefore cannot be read as one side of a randomized or concurrent controlled comparison. Changes relative to a control group are not assessed by this design.
Primary question
The primary question is whether CEUS can assess normal perfusion versus area(s) of hypoperfusion in the heart, kidneys and/or brain in pediatric patients with COVID-19. The primary measure is described as a count of participants, with a 15 minutes timeframe. The record also says the investigators intended to relate imaging findings to clinical outcomes, but those correlations are not reported in the registry record.
3. Trial Design
NCT04640038, titled “Contrast Enhanced Ultrasound in COVID-19,” is registered as a phase 3, completed, single-group study. The official title describes CEUS detection of microvascular perfusion impairment in pediatric patients with COVID-19. The registry lists Children's Hospital of Philadelphia as the sponsor and describes a one-site pilot at The Children's Hospital of Philadelphia. The study start is 2020-12-18, and primary completion is 2021-09-17.
The registered enrollment is 4. The study summary says investigators planned to enroll and evaluate 30 patients. These figures describe the registered enrollment and the plan stated in the summary; they do not establish why enrollment differed. A reason is not reported in the registry record.
Participants received intravenous sulfur hexafluoride lipid-type A microspheres before CEUS. The arm description identifies a weight-based dose, but its final instruction is incomplete in the registry text, so the full administration schedule is not available. Masking is listed as none, and allocation is listed as not applicable. The design is not a randomized comparison, and no like-for-like control group is registered.
The record identifies one primary outcome measure and reports no analyses. The phase designation and the pilot description are both recorded, but the registry does not explain their relationship. It also does not report a protocol justification for the enrollment target, an interim-analysis plan, or a detailed statistical analysis plan. Accordingly, the outcome information should be interpreted as descriptive registry reporting, not as a controlled estimate of an intervention effect.
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.
Overall Study
| Stage | Study Population |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
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 | Study Population |
|---|---|---|
| Participants analysed | 4 | |
| Age, Categorical: <=18 years | Participants | 4 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 7.5 (SD 2.9) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 4 |
| Hospital stay | Days | 7 (4 to 8) |
6. Primary Endpoint
The registry lists the primary outcome as Estimate the Proportion of Patients With Normal Perfusion Versus Area(s) of Hypoperfusion in Heart, Kidneys and/or Brain, measured over 15 minutes..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is framed as the number of participants with normal perfusion versus area(s) of hypoperfusion in the heart, kidneys and/or brain. The assessment uses CEUS in patients with confirmed or probable COVID-19, with a listed timeframe of 15 minutes. This is a participant-level outcome: it concerns how many participants fall into the described perfusion categories, rather than a continuous measurement such as a mean perfusion value.
Assessing perfusion is relevant to the study's stated aim because the registry summary describes concern about microvascular perfusion impairment in COVID-19 and proposes imaging the heart, kidneys and/or brain. The endpoint is intended to characterize imaging findings, not to compare CEUS with another test or to estimate a treatment effect.
The record reports that sufficient diagnostic quality to analyze the ultrasound examination was achieved in three out of four patients. That statement concerns whether images could be analyzed; it is not a numerical result for the proportion with normal perfusion or hypoperfusion. The registry record does not report the category counts, a proportion, or an estimate of clinical-outcome association for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The clearest posted outcome information is about image interpretability: sufficient diagnostic quality to analyze the ultrasound examination was achieved in three out of four patients. This indicates that analyzable examination quality was not documented for every enrolled patient. It does not identify the perfusion category for those with analyzable images, and it does not state whether perfusion was normal or impaired in any particular organ.
The primary endpoint is intended to count participants according to normal perfusion versus area(s) of hypoperfusion. Those category counts are not reported in the registry record. The record lists one outcome measure but no analyses. As a result, there is no reported numerical estimate of the primary perfusion outcome, no uncertainty interval for that outcome, and no reported analysis connecting imaging findings with clinical outcomes. These omissions prevent a quantitative interpretation of the intended primary question.
Enrollment was 4, while the study summary said the investigators planned to enroll and evaluate 30 patients. The available registry text does not explain the difference. With so few enrolled participants, any observed descriptive pattern would need to be interpreted cautiously, but no perfusion-category pattern is reported to characterize. It would not be appropriate to infer a frequency of hypoperfusion from the diagnostic-quality statement.
This is a single-group study with no registered comparator and no masking. It can describe the imaging assessments made in its enrolled participants, but it does not supply a controlled comparison for estimating differences between CEUS and another approach. Nor does it establish that an imaging finding causes a clinical outcome. The planned correlation with clinical outcomes is an aim in the summary, not a result reported in the registry.
The safety figures list zero serious adverse events, zero other adverse events, and zero deaths in the contrast-enhanced ultrasonography group, with 4 participants at risk for each listed category. These are registry counts for this group; they do not by themselves provide a precise estimate of event risk or establish that events cannot occur. Overall, the posted record documents a small pilot experience and a diagnostic-quality observation, while leaving the principal perfusion result and its uncertainty unavailable.
9. Statistical Methods Explained
The primary measure is described as a count of participants. A count is a descriptive way to report how many people meet an outcome definition. Here, the intended categories are normal perfusion and area(s) of hypoperfusion in the heart, kidneys and/or brain. The registry does not give the count in either category. Without those outcome counts, neither a category proportion nor a comparison between categories can be interpreted from the posted results.
What does a confidence interval add?
In general, a confidence interval expresses the precision of an estimate by showing a range of values compatible with the observed data under a specified statistical procedure. Narrower intervals usually indicate greater precision, while wider intervals indicate greater uncertainty. A confidence interval does not make an incomplete or biased measurement reliable, and it does not turn a descriptive result into a causal comparison. The registry record does not report a confidence interval for the primary perfusion outcome.
For a binary outcome, an analysis may describe the number with the outcome and the number assessed, and may estimate the proportion with uncertainty. That approach depends on knowing which participants had an evaluable assessment and how the outcome categories were assigned. The registry reports that sufficient diagnostic quality was achieved in three out of four patients, but does not provide participant-level outcome classifications, a rule for handling examinations that could not be analyzed, or a primary-outcome analysis population. A numerical proportion should therefore not be reconstructed from the quality statement.
Why does the single-group design matter?
General statistical interpretation distinguishes description from comparison. A single-group study can report what was observed among participants assessed with the intervention, but a treatment or test effect usually requires a comparison that addresses what would have happened under an alternative condition. This registry lists no comparator and no random allocation. It therefore does not support a randomized contrast or an estimate of relative performance against another diagnostic approach. The planned relationship between imaging findings and clinical outcomes would also require outcome data and an analysis method; neither is reported in the registry record.
Masking is listed as none. In general, masking can reduce the possibility that knowledge of an intervention or clinical status influences assessment or classification. Its absence does not prove that an assessment was biased, but it makes transparent outcome definitions and assessment procedures important. Those procedural details are not reported in the registry text available for this outcome.
How should the planning assumptions be read?
The stated planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. The registered study, however, is single-group and has no like-for-like control comparison. Those two-arm assumptions do not describe the enrolled study design. The registry record does not report numerical planning estimates that can be interpreted for this study, nor does it report the observed effect values needed to assess such an illustration. Any sample-size illustration is a planning exercise, not observed power and not evidence that the study had adequate power.
In general, statistical power is a design property tied to assumed effects, variability, significance criteria, and analysis methods. It is not a measure of how likely the observed result is true. Since the record does not report a power calculation for the registered single-group design or a primary analysis result, no conclusion about power can be drawn from the enrollment alone. The planned enrollment of 30 is stated in the study summary, but its statistical justification is not reported in the registry record.
What about sparse or over-dispersed data?
For count outcomes, general models may need to account for over-dispersion when the observed variability exceeds what a simpler model assumes. That issue matters when there are enough outcome observations to assess variability and when a count model is appropriate. This endpoint is described as a count of participants, and the registry supplies no category counts or model results. There is therefore no basis for assessing over-dispersion or selecting a more elaborate count model for the posted result. The limited outcome reporting, rather than a particular model choice, is the central constraint on interpretation.
In short, the record gives the endpoint's intended meaning and a diagnostic-quality statement, but not the primary outcome values, uncertainty estimates, or analysis details. General statistical principles can explain what such analyses would convey, but they cannot substitute for results that are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and no analyses. A single listed primary endpoint can limit some concerns about testing many primary outcomes, but the record does not establish whether additional outcomes or exploratory analyses were conducted outside the posted information. A multiplicity strategy, including any adjustment or prioritization among outcomes, is not reported in the registry record. Without reported analyses, it is not possible to assess how many statistical tests were performed or how their results were interpreted.
The record reports sufficient diagnostic quality in three out of four patients, but does not explain how examinations without sufficient quality were handled in the primary endpoint analysis. It does not report whether all enrolled participants were included in an analysis population, how missing or unevaluable outcomes were treated, or whether any imputation or sensitivity analysis was used. The category counts for normal perfusion and hypoperfusion are also absent, so the evaluable denominator for those categories is not available.
The registry does not report an interim-analysis plan, a detailed statistical analysis plan, or a definition of analysis populations. It also does not explain whether the intended clinical-outcome correlations were prespecified or exploratory. These details matter because they clarify which observations contribute to an estimate and how much confidence to place in reported findings. In their absence, interpretation should remain limited to the diagnostic-quality statement and the posted safety counts.
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 |
|---|---|---|---|
| Contrast-enhanced Ultrasonography | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Contrast-enhanced Ultrasonography | 0 of 4 |
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 |
|---|---|
| Contrast-enhanced Ultrasonography | 0 of 4 |
For the contrast-enhanced ultrasonography group, the registry lists 4 participants at risk for serious adverse events and 0 affected. It lists 4 at risk for other adverse events and 0 affected, and 0 deaths. No serious adverse-event terms are listed. These figures describe the events recorded for this group in the registry.
A zero count means that no event in the corresponding category is reported among the participants at risk; it does not prove that the event risk is zero in a broader population. The small enrollment limits how precisely these counts can characterize uncommon events. The record does not report a comparative safety analysis, a separate control group, or additional detail about the timing and ascertainment of these events. The figures should therefore be read as descriptive counts, not as proof of safety or as a comparison against another intervention.
12. What the Result Does, and Does Not, Mean
The record documents a pilot assessment of CEUS for examining microvascular perfusion in pediatric patients with confirmed or probable COVID-19. It reports that sufficient diagnostic quality to analyze the ultrasound examination was achieved in three out of four patients. This is useful descriptive information about image analyzability in the enrolled group.
The record does not report how many participants had normal perfusion or area(s) of hypoperfusion, despite that being the primary endpoint. It also does not report a numerical relationship between imaging findings and clinical outcomes. Consequently, the posted information does not establish the frequency of perfusion impairment in this group, the precision of such a frequency, or whether imaging findings tracked clinical outcomes.
The study has no registered comparator, and the design is not randomized. The findings cannot be interpreted as a comparative estimate of CEUS performance against another diagnostic method, and they do not establish a causal effect. The registry's summary describes the intended use of imaging and the rationale for studying perfusion, but rationale is not outcome evidence.
The safety registry counts are also descriptive. No serious adverse events, other adverse events, or deaths are listed for the enrolled group, but those counts do not demonstrate that such events cannot occur or establish risk in a broader population. The enrollment of 4 and the absence of reported primary outcome values impose substantial limits on what can be concluded. The most defensible reading is that the registry records a small pilot, an image-quality observation, and safety counts, while leaving the central perfusion result unresolved in the posted record.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it separates the feasibility of obtaining analyzable images from the clinical question the imaging was intended to address. The registry reports sufficient diagnostic quality in three out of four patients. That observation concerns whether the examination could be analyzed; it does not answer how many participants had normal perfusion or hypoperfusion. Keeping these outcomes distinct prevents an image-quality finding from being mistaken for a disease-frequency estimate.
The record also illustrates why outcome definitions and analysis details matter. A count of participants requires clear classification rules and an account of who could be evaluated. The registry gives the broad endpoint and a diagnostic-quality statement, but does not report the perfusion-category counts or how unevaluable examinations were handled. Without those details, neither a point estimate nor its uncertainty can be assessed.
Design and planning assumptions must also align. This is registered as a single-group study, while the stated planning assumptions refer to equal allocation between two arms. Such assumptions cannot be read as a description of the study's actual comparison structure. More generally, a planning calculation cannot replace observed data or a reported analysis.
Finally, the enrollment is 4, compared with a planned enrollment of 30 stated in the study summary. That difference makes transparent reporting of the achieved sample, missing assessments, and endpoint results especially important. The posted record allows readers to identify what was measured and what was not reported, which is essential for setting appropriate limits on statistical interpretation.
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 central limitation is that the numerical primary perfusion outcome is not reported in the registry record. The stated endpoint concerns normal perfusion versus area(s) of hypoperfusion, but no category counts, proportions, or uncertainty estimates are posted. The available diagnostic-quality statement cannot substitute for these outcomes.
Enrollment was 4, while the study summary states a planned enrollment of 30. The registry does not explain the difference or report the rationale for the target enrollment. The small enrolled group limits the precision and breadth of descriptive conclusions, and there is no reported sample-size justification for the registered single-group design.
The study has no comparator, no random allocation, and no masking. It is therefore not suited to a controlled estimate of relative diagnostic performance or a causal effect. The record also does not provide the full administration schedule, detailed image-assessment procedures, an analysis population, rules for unevaluable images, or a detailed statistical analysis plan. The arm description ends with an incomplete instruction.
The registry says investigators intended to correlate imaging findings with clinical outcomes, but does not report those correlations. The duration and completeness of outcome ascertainment, handling of missing data, and any interim analyses are not reported in the registry record. These limitations mean that the posted information supports only a narrow descriptive reading of image quality and safety counts, not a comprehensive assessment of the primary perfusion question.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Contrast Enhanced Ultrasound in COVID-19 — NCT04640038.
- Registry record last updated 2024-07-30; status last verified 2024-07.
- Results first posted 2024-03-08.
- 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
NCT04640038 is a completed, phase 3, single-group study sponsored by Children's Hospital of Philadelphia. It evaluated CEUS with intravenous sulfur hexafluoride lipid-type A microspheres to assess microvascular perfusion in pediatric patients with confirmed or probable COVID-19. The registry lists enrollment of 4 and states that the study summary planned to enroll and evaluate 30 patients.
The primary endpoint concerns normal perfusion versus area(s) of hypoperfusion in the heart, kidneys and/or brain, with a 15 minutes timeframe. Sufficient diagnostic quality to analyze the ultrasound examination was achieved in three out of four patients. The perfusion-category counts and analyses are not reported in the registry record. The safety record lists 0 serious adverse events, 0 other adverse events, and 0 deaths. With no comparator and no numerical primary outcome result, interpretation remains descriptive and limited.