Visualization of Cerebral Arteries Using Contrast-Enhanced Transcranial Ultrasound in Stroke Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Visualization of Cerebral Arteries Using Contrast-Enhanced Transcranial Ultrasound in Stroke Patients (NCT00282841), a na na study. The primary outcome is Number of Participants With Successful Visualization of the Intracranial Arteries in Comparison to Reference Method (MRA/CTA).

2. Clinical Question

In general, a diagnostic visualization study asks whether an index method can show the target anatomy when assessed against a reference method. That question is distinct from whether an intervention improves a health outcome. The registry record describes visualization of cerebral artery segments and identifies participants as the outcome unit in the title. The exact rule for translating segment-level assessments into a participant-level success result is not reported in the registry record.

The study's single-group structure means the clinical question is not a comparison of ultrasound against a concurrent randomized control group. Instead, the ultrasound assessment is considered in relation to CTA or MRA. The record does not report a numerical estimate of agreement, sensitivity, or another diagnostic performance measure.

3. Trial Design

The registry record describes a single-group study of contrast-enhanced transcranial ultrasound in stroke code patients. Allocation is listed as NA, masking as none, and the study model as single group. These entries do not describe a randomized treatment comparison. The listed intervention is ultrasound, classified as OTHER.

The arm description states that, after written informed consent, Code Stroke patients would undergo a contrast-enhanced transcranial ultrasound study to visualize intracranial arteries. It names intravenous administration of Definity and application of transcranial ultrasound via the temporal approach. The procedural description ends before all details are given, so further information about the examination is not reported in the registry record.

The primary outcome compares ultrasound visualization with CTA or MRA. It records successful visualization as yes or no, and its timeframe is within 24 hours after the reference method. The outcome description says an experienced sonographer assessed visualization while blinded to the cerebral MRA/CTA. This endpoint-specific blinding statement can coexist with the overall masking entry of none: the record does not describe masking of participants or the study as a whole, but it does report that the sonographer was unaware of the reference imaging.

The registry record lists enrollment of 61 and identifies the sponsor as the University of California, San Diego. The study start is recorded as 2005-03 and primary completion as 2007-10. Its status is TERMINATED. The reason for termination, whether the planned enrollment was reached, and details of any changes to the design are not reported in the registry record.

Phase is listed as NA. The registry record lists one outcome measure and zero analyses. The latter means no analysis is listed in the record; it does not by itself establish what analyses may have been conducted outside the registry. No protocol rationale, sample-size justification, interim-analysis plan, or detailed statistical analysis plan is reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: Based on the assumption that all target intracranial vessel segments could be visualized with either one of the reference methods, CTA or MRA, in all patients enrolled, the transcranial ultrasound data was analyzed to assess how many of the target vessel segments could be visualized in comparison to the reference method.

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 Number of Participants With Successful Visualization of the Intracranial Arteries in Comparison to Reference Method (MRA/CTA), measured over within 24 hours after reference method.

The primary endpoint is titled as the number of participants with successful visualization of intracranial arteries in comparison with a reference method, MRA or CTA. The unit is participants, the parameter is NUMBER, and the timeframe is within 24 hours after the reference method. The description says successful visualization of cerebral artery segments was assessed as yes or no by an experienced sonographer blinded to the cerebral MRA/CTA.

Visualization is relevant to the study's stated purpose because the ultrasound examination was intended to show intracranial arteries and the reference imaging supplies a basis for comparison. In general, a clearly defined visualization outcome can describe whether the target anatomy was seen under the study's examination conditions. A reference-method comparison can also help readers understand how an imaging assessment relates to another imaging method, provided the assessment rules and results are reported.

The registry record does not report how many participants met the success definition, how many did not, or the specific criteria for deciding that visualization was successful. The title frames the outcome at the participant level, while the description refers to cerebral artery segments. How segment-level findings were combined into a participant-level result is not reported in the registry record. No estimate of diagnostic accuracy or agreement is listed among the analyses.

Without the outcome counts and a fuller definition of success, the primary endpoint cannot be interpreted quantitatively from the registry record. Its stated purpose and assessment method can be described, but the magnitude or precision of any observed result cannot be established.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record lists one primary outcome measure but zero analyses. It defines the outcome as a number of participants with successful visualization, assessed yes or no, in comparison with CTA or MRA. No numerical result, statistical estimate, confidence interval, or test result is reported. The methods discussion below explains general concepts that can help interpret this type of endpoint; it does not describe analyses that the record says were performed.

What does a binary outcome represent?

In general, a binary outcome places each assessed unit into one of two categories, such as success or no success. If the unit is a participant, the result can be expressed as a count in each category or as a proportion, when the relevant denominator is known. For this study, the endpoint title names participants as the unit, and the description says visualization was assessed yes or no. The registry does not report the category counts or the exact participant-level success rule.

The description also refers to cerebral artery segments. In general, several segment assessments within one participant are not automatically equivalent to several independent participant observations. A participant-level endpoint might require a rule for combining segment findings, such as whether success requires visualization of particular segments or all target segments. The specific rule is not reported in the registry record. Without it, readers cannot determine exactly how the stated yes/no participant outcome was derived from the segment assessments.

How does a reference-method comparison work?

In general, a diagnostic or imaging comparison evaluates an index method in relation to a chosen reference method. Here, the registry identifies transcranial ultrasound as the examination of interest and CTA or MRA as the reference. A comparison can be summarized in different ways depending on the endpoint and available data. For example, a study may report whether the index method visualized the target, or it may report agreement or diagnostic accuracy. The registry record reports a visualization outcome but does not list an agreement measure, sensitivity, specificity, or other analysis.

A reference method is not necessarily a perfect representation of the underlying condition. Interpretation depends on how the reference was selected and applied, and on whether assessments are made independently. The registry says the sonographer was blinded to the cerebral MRA/CTA, which is relevant to independent assessment. It does not report the choice process for CTA versus MRA, the assessment protocol in detail, or how discrepant or indeterminate findings were handled.

Why do the time and blinding details matter?

The timeframe is stated as within 24 hours after the reference method. In general, timing helps define which examinations are considered comparable. If anatomy or clinical status changes between assessments, the interval may affect whether the methods are evaluating the same state. The registry record does not report the actual intervals for participants or whether the interval was consistent.

The record describes an experienced sonographer who was blinded to the reference imaging. In general, blinding can reduce the influence of expectations on an assessment. It does not by itself ensure that the test is accurate or that assessments are reproducible. The registry does not report whether multiple sonographers assessed images, how reproducibility was measured, or whether the assessor could be blinded to other clinical information.

What can an estimate and confidence interval tell readers?

In general, an estimate is a numerical summary of the observed data. A confidence interval communicates the uncertainty associated with that estimate under a specified statistical model and sampling assumptions. A narrow interval indicates more precision than a wide interval, but neither the estimate nor the interval alone resolves questions about study design, measurement quality, or generalizability. Because the registry record does not report a primary outcome estimate or confidence interval, the precision of the study's result cannot be assessed.

For a binary endpoint, the choice of summary depends on the question. A count describes how many observations fell into a category; a proportion describes the frequency relative to a defined denominator. In a comparison against a reference method, paired classifications can support measures of agreement or diagnostic performance if the underlying results are available and the analysis is specified. No paired-result data or such measures are reported in the registry record. No new effect estimate can be derived from enrollment alone.

How should sample-size planning be read?

In general, sample-size planning estimates how much information a future study may need for a chosen design, target effect, and statistical assumptions. It is not a result about what happened in a completed or terminated study. The stated planning assumptions describe 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. This is a planning illustration, not a description of the registry's single-group design. The registry record does not report a trial-specific sample-size justification or numerical planning values.

Planning based on an observed effect can be sensitive to uncertainty in that effect. In general, an effect estimated from a study may not be stable, particularly when the available information is limited. A planning illustration should therefore not be described as observed power, and it cannot replace reporting the trial's actual outcome estimate and its uncertainty. No numerical planning results or observed effect are reported in the registry record.

What does over-dispersion mean in general?

Over-dispersion is a general statistical concept for data whose variability is greater than a model expects. It can arise when observations are more heterogeneous or more dependent than the model allows. Accounting for over-dispersion may affect uncertainty estimates in analyses where it applies. The registry record does not report an over-dispersion analysis, and the listed binary participant-level outcome does not establish that such a model was used or needed.

More broadly, statistical methods depend on the data structure and the question being asked. Segment-level observations may be clustered within participants, while a participant-level yes/no outcome has a different structure. The registry record does not report the analysis dataset, the handling of segment-level measurements, or any model specification. Those omissions prevent a reader from reconstructing an analysis or checking its assumptions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Stroke Code Patients - Reference Method", "Stroke Code Patients - Transcranial Ultrasound")
n      <- c(61, 61)
events <- c(8, 8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Stroke Code Patients - Reference Method  61  8  13.1  5.8  24.2  6.8  23.8  6.9  23.9
ARM  Stroke Code Patients - Transcranial Ultrasound  61  8  13.1  5.8  24.2  6.8  23.8  6.9  23.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It identifies a primary outcome, but does not report a statistical analysis plan, an analysis population, or results. It is therefore not possible to determine from the record whether additional outcomes or exploratory analyses were conducted outside the registry entry.

In general, multiplicity arises when several hypotheses or outcomes are tested, increasing the chance of at least one false-positive finding if each test is interpreted without accounting for the others. Methods for handling multiplicity depend on the number and relationship of the tests and on which outcomes were designated primary. The registry record does not report a multiplicity strategy. With no analyses listed, there is no reported set of tests whose multiplicity adjustment can be evaluated.

The record does not report missing-data counts or explain how missing, unreadable, or indeterminate imaging assessments were handled. It also does not report whether all enrolled participants underwent both ultrasound and a reference examination or were included in the primary outcome analysis. The enrollment entry is not, by itself, an analysis denominator.

In general, missingness can affect interpretation when participants with unavailable assessments differ from those with complete data. A complete-case analysis, an imputation approach, and other methods rely on different assumptions. No method is specified in the registry record, so the effect of missing observations cannot be assessed. The record also does not define an analysis population, such as all enrolled participants or only those with paired assessments.

The listed planning assumptions concern a hypothetical two-arm design, while the registry describes a single-group study. They should not be treated as an analysis plan for this trial. A trial-specific plan for multiplicity, missing data, or analysis populations is not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

For the Stroke Code Patients group, the registry lists 61 participants at risk for serious adverse events and zero affected. It also lists 61 at risk for other adverse events and zero affected. No serious adverse-event terms are listed. The death value is not reported in the registry record.

These entries describe the counts recorded in the registry; they do not demonstrate that the true risk of an adverse event is zero. In general, a zero event count means no events were recorded in the stated data, while the possibility of events beyond the observed record cannot be ruled out. The registry does not report how adverse events were defined, how they were monitored, the duration of safety follow-up, or whether safety information was complete for all participants.

The serious and other adverse-event categories should be read separately as recorded. The registry entries do not describe event severity beyond the serious-event classification, nor do they provide event narratives or a comparison group. Because this is a single-group study, these counts do not support a comparative safety estimate. The registry record also does not explain why the study was terminated, so termination should not be attributed to safety concerns on the basis of these entries.

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

The registry record establishes that the study was designed to assess whether contrast-enhanced transcranial ultrasound could visualize intracranial arteries in stroke code patients in comparison with CTA or MRA. It identifies a yes/no visualization outcome, a participant-level unit in the outcome title, and an assessment by an experienced sonographer reported to be blinded to the reference imaging. It does not report the outcome results or an analysis.

As a result, the posted record does not show how many participants had successful visualization or how the ultrasound assessments related numerically to the reference method. It cannot support a numerical conclusion about the frequency of successful visualization, agreement, or diagnostic accuracy. No confidence interval or other measure of precision is reported. The absence of a posted result is not evidence that the examination succeeded or failed.

The single-group design is important to the scope of interpretation. This study is not described as a randomized comparison of ultrasound with a control group, and its primary outcome concerns visualization rather than a clinical outcome. Any result from this design would address the stated imaging question under the study's assessment conditions; it would not, by itself, establish effects on patient health or compare treatment strategies.

Several details needed for a fuller interpretation are not reported in the registry record: the participant-level success rule, the handling of segment assessments, the actual comparison results, missing-assessment handling, and the reason for termination. The record also does not report how CTA or MRA was selected or the actual timing of each examination. These gaps limit both reproducibility and assessment of possible sources of bias.

The safety entries report zero serious and zero other adverse events in the listed group, but do not establish that the risk of harm is absent. They are separate from the missing visualization outcome and cannot fill the gap in diagnostic results. Overall, the registry record describes the study question and some design features, but does not provide enough outcome information to quantify what the study found.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a stated imaging question and the result information available in the registry. The record defines a primary visualization outcome and names a reference method, but lists zero analyses and does not report the outcome count. A well-defined question is necessary for interpretation, but a question alone cannot establish the observed frequency or precision of a result.

The endpoint also raises a measurement issue that is common in imaging research. The title describes a participant-level count, while the outcome description refers to cerebral artery segments. In general, measurements at a lower level, such as segments within a participant, may require a prespecified rule before they can be combined into a participant-level outcome. Without the rule, readers cannot know exactly what constitutes participant-level success or reconstruct the outcome from segment assessments.

The reference-method structure makes assessment procedures relevant. The registry reports that the sonographer was blinded to the cerebral MRA/CTA, a detail that can matter when an outcome involves human judgment. However, the record does not give the detailed assessment criteria, results, or handling of uncertain findings. Thus the design description identifies some safeguards but does not allow a complete evaluation of measurement reliability or diagnostic performance.

The registry's single-group design also matters for the interpretation of planning information. The stated sample-size assumptions describe equal allocation between two arms, while the study is listed as single group. Planning illustrations based on those assumptions are not the study's design or a trial-specific justification. Keeping design descriptions separate from planning calculations prevents a hypothetical framework from being mistaken for an observed comparison.

Finally, the status TERMINATED and the safety counts are not explanations of the missing outcome analysis. The reason for termination is not reported, and zero recorded adverse events do not supply information about visualization performance. The record therefore illustrates why outcome reporting, analysis definitions, and transparent handling of missing information are essential for readers to assess evidence.

15. 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 primary limitation for interpretation is that the registry record does not report the primary outcome count or any analysis. Without outcome results, the frequency of successful visualization and its precision cannot be assessed. The record also does not report the result of the comparison with CTA or MRA.

The endpoint definition is incomplete for reproducibility. The title names participants as the unit, whereas the description refers to visualization of cerebral artery segments. The criteria for success, the target segments, and the rule for translating segment assessments into participant-level outcomes are not reported in the registry record. The description of the study procedure is also incomplete.

The record does not say how the reference method was selected, whether participants had CTA or MRA, or whether both were used. It gives the assessment window as within 24 hours after the reference method but does not report actual examination intervals. Details of handling indeterminate, unreadable, or missing assessments are not reported.

Although the outcome description says the sonographer was blinded to the reference imaging, the registry does not report how blinding was implemented or whether it was maintained. The listed overall masking status is none. The record also does not report independent duplicate assessments or reproducibility measures.

The study status is TERMINATED, but the reason is not reported. The record does not establish whether the listed enrollment was the final analyzed population. It also does not report eligibility criteria beyond identifying stroke code patients, or provide details that would allow assessment of how broadly the enrolled group represents other settings.

Finally, the record lists no analyses, gives no statistical analysis plan, and does not specify analysis populations or missing-data methods. The safety entries have limited detail, with no listed serious adverse-event terms and no reported death count. These limitations constrain conclusions about the outcome, its precision, and the completeness of safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Visualization of Cerebral Arteries Using Contrast-Enhanced Transcranial Ultrasound in Stroke Patients — NCT00282841.
• Registry record last updated 2019-08-07; status last verified 2019-07.
• Results first posted 2019-08-07.
• 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.

19. Record Summary

The registry record describes a terminated, single-group study of contrast-enhanced transcranial ultrasound in stroke code patients. It lists enrollment of 61, with the University of California, San Diego as sponsor. The study start is recorded as 2005-03 and primary completion as 2007-10. Allocation is NA, masking is none, and phase is NA.

The primary outcome concerns successful visualization of intracranial arteries in comparison with CTA or MRA. The stated timeframe is within 24 hours after the reference method, and the description says an experienced sonographer assessed visualization while blinded to the reference imaging. The record lists one outcome measure and zero analyses.

No primary outcome count or analysis result is reported in the registry record. The safety entries list zero serious and zero other adverse events among 61 participants at risk in the Stroke Code Patients group. No serious adverse-event terms are listed, deaths are not reported, and the reason for termination is not reported.