tSCI Contrast Enhanced Ultrasound Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for tSCI Contrast Enhanced Ultrasound Study (NCT04056988), a na phase 4 study. The primary outcome is Feasibility of Intraoperative Contrast-enhanced Ultrasound in Acute Traumatic Spinal Cord Injury - Number of Participants With Successful Intraoperative Contrast-enhanced Ultrasound in Acute Traumatic Spinal Cord Injury.

2. Clinical Question

3. Trial Design

The registry record describes a PHASE4, single-group study of intraoperative CEUS in acute traumatic spinal cord injury. It lists University of Washington as the sponsor, enrollment of 27, a start date of 2018-07-31, primary completion on 2023-11-20, and status as completed. Allocation is listed as not applicable, and masking as none. These features describe a study without a separate randomized control group.

The intervention is perflutren lipid microsphere, identified as an ultrasound contrast agent. The study aimed to use CEUS during the decompressive surgery required by participants to assess perfusion at the injury site. The registry describes the primary endpoint as successful intravenous administration of the contrast agent together with acquisition of interpretable intraoperative CEUS perfusion imaging.

Because the design is single-group, the primary feasibility outcome is a count among participants undergoing the procedure, rather than a contrast between treatment arms. The record does not report a comparator intervention, a control group, or a masking procedure beyond listing masking as none. The number who completed the assessment or were included in an endpoint analysis is not reported in the registry record.

The registry gives a timeframe of the operative period to one-week or hospital discharge, whichever occurred first, for the primary endpoint. Further details of the study protocol, including eligibility criteria beyond the acute injury context, are not reported in the registry record. The recorded completion status indicates that the study is marked completed; it does not, by itself, provide the endpoint result.

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 approved for a total of 80 patients during the approval/funding period. 27 subjects were recruited to the study, with a total of 22 completing the study. 5 subjects succumbed to their injuries, not related to the study. Subjects were enrolled in the study when the inclusion criteria were met and consent was obtained. Actual enrollment did not meet the approved, anticipated enrollment number during the study.

Overall Study

Reasons for not completing this period:

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: Acute, severe spinal cord injury requiring surgery.

6. Primary Endpoint

The registry lists the primary outcome as Feasibility of Intraoperative Contrast-enhanced Ultrasound in Acute Traumatic Spinal Cord Injury - Number of Participants With Successful Intraoperative Contrast-enhanced Ultrasound in Acute Traumatic Spinal Cord Injury, measured over Operative period to one-week or hospital discharge (first occurring event).

The primary endpoint is the number of participants with successful intraoperative CEUS in acute traumatic spinal cord injury. Success is defined as both successful intravenous administration of perflutren lipid microsphere and acquisition of interpretable CEUS perfusion imaging during spinal decompressive surgery. The specified assessment period runs from the operative period to one-week or hospital discharge, whichever occurs first.

This endpoint is used to assess whether the procedure and imaging can be carried out under the conditions of the operation. A feasibility measure is different from a clinical outcome: it records whether the specified imaging steps were completed successfully, rather than whether a participant’s spinal cord blood flow or later function improved. The registry’s study rationale describes assessing blood flow at the injury site, but the primary endpoint is defined by administration and image interpretability.

The record does not report the number of participants meeting the success definition, the number assessed, or a numerical endpoint estimate. It therefore does not establish the frequency of successful imaging from the posted endpoint information. Reasons for unsuccessful or unavailable imaging, if any, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines the primary outcome as a count of participants meeting a binary success definition. In general, a binary outcome classifies each assessed participant into one of two categories. Here, success requires both intravenous contrast administration and interpretable intraoperative perfusion imaging. This combined definition matters: completing only one of those steps would not meet the stated definition.

What does a count tell us?

A count gives the number of participants meeting an outcome definition. To interpret how common an outcome was in a study group, the count needs a relevant denominator: the number of participants whose outcome could be assessed. In this record, enrollment is 27, but the number evaluated for the primary endpoint and the number meeting its definition are not reported in the registry record. Enrollment should not automatically be treated as the endpoint denominator, because the registry does not state that every enrolled participant had an evaluable result.

A proportion can describe the frequency of success in an assessed group, while an uncertainty interval can express how imprecise that estimate may be. In general, an interval reflects the range of values compatible with the observed data under the method used. It does not resolve missing endpoint information: without a reported count and denominator, neither an estimate nor its interval can be reconstructed. No confidence interval for the primary endpoint is reported in the registry record.

Why does the single-group design matter?

A single-group study can describe whether a procedure was completed and whether its imaging met an operational definition in the participants studied. It cannot, by itself, separate the effect of the procedure from other influences or estimate a comparative effect against a control group. A randomized comparison would address a different question by comparing outcomes across assigned groups. This registry record lists a single-group model, allocation as not applicable, and no masking; it does not describe a like-for-like control comparison.

The primary endpoint is a feasibility endpoint, not a direct measure of improvement in spinal cord perfusion or functional outcome. Such distinctions are important because the study rationale and the measured outcome are not interchangeable. The rationale describes why information about hypo-perfusion may matter; the recorded primary endpoint asks whether contrast administration and interpretable imaging were achieved during surgery.

What analysis plan is reported?

The statistical analysis plan, including any hypothesis test or estimation method for the primary outcome, is not reported in the registry record. The record also does not report a feasibility threshold, a confidence-interval method, or a prespecified handling rule for participants without an interpretable image. No sample-size justification for the trial is reported in the registry record.

A separate planning illustration is described as 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 fraction of the observed effect. Those are planning assumptions, not evidence that this study had two arms: the trial itself is recorded as single-group. No resulting planning values are included in the record details, and the illustration is not an observed-power analysis. Planning calculations answer hypothetical design questions; they do not supply an unreported trial outcome.

How should missing information be treated?

When some participants lack an endpoint assessment, the denominator and the handling of those participants can affect interpretation. A complete-case description, an assumption that missing outcomes count as failures, or another approach would answer the question differently. The registry record does not state how missing or uninterpretable assessments were handled, nor does it report an analysis population. It would therefore be inappropriate to assume that all enrolled participants were analyzed or to assign outcomes to participants whose results are not reported.

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("Acute Spinal Cord Injury Patients to Undergo Contr")
n      <- c(27)
events <- c(27)
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  Acute Spinal Cord Injury Patients to Undergo Contr  27  27  100.0  87.2  100.0  87.5  100.0  87.7  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and one analysis. It does not report a multiplicity adjustment or a broader testing hierarchy. With only one listed primary outcome, a multiplicity procedure may not be central to interpreting that endpoint, but the complete statistical analysis plan is not reported in the registry record. The record does not establish whether additional exploratory analyses were planned or conducted.

Missing-data handling is also not reported in the registry record. The study enrolled 27 participants, but the number with an evaluable primary outcome is not given. The record does not say whether every participant received the contrast agent, whether every image was interpretable, or how participants without an assessable endpoint were treated analytically. Those details are important because the endpoint is defined by completion of two linked steps.

The analysis population is not reported in the registry record. It is therefore not possible to determine whether the endpoint was analyzed among all enrolled participants, among participants who underwent surgery, or among a different set of participants. The registry does not report a protocol-defined analysis population or a method for handling departures from the planned procedure.

These are reporting gaps, not proof that the study lacked procedures for multiplicity or missing data. They prevent readers from assessing the consequences of those choices in the posted results. No assumptions about missing outcomes or unreported analyses should be substituted for the absent information.

12. 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.

The safety fields list 27 participants at risk for serious adverse events and 0 serious adverse events. They also list 27 participants at risk for other adverse events and 0 other adverse events. Deaths are reported separately as 5. These are distinct registry fields and should be read as recorded rather than combined into a single outcome.

The adverse-event timeframe, event definitions, causes of death, and relationship of any event or death to the procedure or contrast agent are not reported in the registry record. The separate death count does not establish that the deaths were caused by the study intervention, and the zero event counts do not explain how death information was handled in the other fields. No causal conclusion can be drawn from these counts alone.

The counts also do not answer the primary feasibility question. Safety reporting concerns adverse events and deaths; feasibility concerns administration of contrast and interpretability of imaging. The record does not provide participant-level detail or further context for either set of outcomes.

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

The registry record identifies a clinically focused technical question: whether CEUS could be performed during decompressive surgery for acute traumatic spinal cord injury, with successful contrast administration and interpretable perfusion imaging. That makes the primary endpoint relevant to the practical use of an imaging procedure in the operative setting. However, the record does not report the number of participants who met the endpoint definition, so it does not show how often the specified procedure was feasible in this study.

The endpoint should not be interpreted as evidence of improved spinal cord blood flow or better functional outcomes. It measures successful completion of the imaging steps, not a treatment effect. The study rationale describes potential interest in evaluating perfusion, but a rationale is not an outcome result. The posted endpoint information does not quantify perfusion changes or later function.

The design is single-group, with no separate comparator. Thus, even a reported feasibility count would describe performance in the studied group rather than establish superiority or equivalence relative to another approach. The record also does not report a numerical comparison with any clinical threshold or standard.

The safety fields record 0 serious adverse events and 0 other adverse events among 27 at risk in each category, and 5 deaths separately. Without further information on timing, cause, definitions, and relatedness, these figures do not establish why the events occurred or whether they were connected with CEUS.

In practical terms, the registry record documents the study’s objective, design, endpoint definition, enrollment, and selected safety counts, but it does not provide the primary feasibility result. The main quantitative conclusion is therefore limited: the outcome was defined, but its observed value is not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why feasibility outcomes require clear operational definitions. Here, success depends on two linked components: intravenous administration of the contrast agent and acquisition of interpretable intraoperative CEUS perfusion imaging. Defining both components specifies what counts as successful performance, rather than relying on an informal judgment that imaging was attempted.

It also illustrates the difference between a study aim and a reported result. The registry describes a rationale involving spinal cord perfusion after traumatic injury, but the primary endpoint is whether the imaging procedure could be completed as specified. A technically successful image may be useful for evaluating a method, but it is not by itself a measure of a clinical benefit.

Statistically, a feasibility count needs an outcome denominator and a clear account of participants whose outcomes could not be assessed. The registry reports enrollment of 27 but does not report the primary success count, the number assessed, or how missing and uninterpretable results were handled. As a result, the central descriptive estimate cannot be evaluated from the posted endpoint information.

The single-group design is also important to the scope of interpretation. It can address whether an imaging procedure was carried out in the study setting, but it does not provide a direct comparative estimate. The record’s completed status and safety counts do not fill the gap in the primary outcome result. Clear reporting of the count, denominator, uncertainty, and handling of non-evaluable cases would be needed to quantify the stated feasibility question.

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 interpreting the endpoint is that its observed count and analysis denominator are not reported in the registry record. Although the record lists enrollment of 27 and defines successful CEUS, it does not state how many participants met that definition or how many had an assessable result. No endpoint estimate or confidence interval is available in the posted results.

The registry also does not report the reasons for any unsuccessful or uninterpretable imaging, if such cases occurred. This matters because technical feasibility can depend on whether contrast administration was completed, whether images were interpretable, and whether both conditions were satisfied. The record provides no participant-level breakdown of these components.

The single-group design has no control group for comparison, and masking is listed as none. The study therefore cannot provide a randomized estimate contrasting CEUS with another approach. The primary endpoint is procedural feasibility rather than a clinical outcome, and later functional outcomes are not reported as the primary measure.

Additional limitations include the absence of a reported statistical analysis plan, sample-size justification, endpoint missing-data approach, and analysis population. The registry does not report a feasibility threshold or the uncertainty method planned for the primary outcome. The safety fields provide counts but not causes, timing, or relatedness for the separately reported deaths. These limits constrain interpretation of both the feasibility and safety information; they do not establish that unreported procedures were absent from the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: tSCI Contrast Enhanced Ultrasound Study — NCT04056988.
• Registry record last updated 2026-07-13; status last verified 2026-07.
• Results first posted 2026-04-29.
• 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 completed, PHASE4, single-group study sponsored by University of Washington, with enrollment of 27. The listed start date is 2018-07-31 and the primary completion date is 2023-11-20. The study examined intraoperative CEUS using perflutren lipid microsphere during decompressive surgery for acute traumatic spinal cord injury.

The primary outcome is the number of participants with successful CEUS, defined by successful intravenous contrast administration and acquisition of interpretable intraoperative perfusion imaging. Its timeframe is the operative period to one-week or hospital discharge, whichever occurred first. The number meeting the endpoint and the number assessed are not reported in the registry record.

Safety fields list 0 serious adverse events and 0 other adverse events among 27 at risk for each category, with 5 deaths reported separately. Further safety context and the primary feasibility result are not reported in the registry record.