Sonothrombolysis in Patients With STEMI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sonothrombolysis in Patients With STEMI (NCT03092089), a na phase 2 study. The primary outcome is Number of Participants With Spontaneous Reperfusion.

2. Clinical Question

The study also lists post-PCI ST-segment resolution, left ventricular ejection fraction, wall motion score index, and microvascular perfusion score index among its secondary outcomes. These measures address different aspects of reperfusion and cardiac function, but their results are not reported in the registry record. The study question is therefore clinically focused, while the available registry information does not establish the frequency of spontaneous reperfusion or how any measured outcome compares with an alternative approach.

3. Trial Design

This is a prospective, single-group phase 2 study, registered as completed. Enrollment was 15. The record gives a start date of 2017-08-15 and a primary completion date of 2019-10-03. The sponsor is Harald Becher. The study concerns patients with ST-segment Elevation Myocardial Infarction, and the arm description specifies adults presenting with high-risk STEMI.

Participants in the single arm were to receive sonothrombolysis with Definity in addition to standard care, identified as reperfusion therapy with PPCI. The registry also lists myocardial contrast echocardiography. The record lists masking as none and allocation as not applicable. Together with the single-group model, these features mean the design does not include a randomized comparator arm. The observations can describe the enrolled group, but cannot by themselves isolate the effect of sonothrombolysis from standard care, participant characteristics, or other influences on outcomes.

The study summary states that it evaluates possible effects on spontaneous reperfusion, microvascular obstruction, left ventricular function, and infarct size. The primary endpoint is a participant count based on pre-PCI ECG evidence of complete ST-segment resolution. The listed secondary measures include post-PCI ST-segment resolution, echocardiographic left ventricular ejection fraction, wall motion score index, and microvascular perfusion score index. The registry lists nine outcome measures overall, but does not report results for these measures in the record.

The registry identifies the study as phase 2 and completed, but does not report the protocol details needed to judge how outcomes were collected, how the analysis population was defined, or how the study was intended to support later research. A sample-size justification for the trial is not reported in the registry record. The record also does not report an interim analysis plan or a statistical analysis plan.

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: for patients did not have a pre PCI ECG

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 Spontaneous Reperfusion, measured over Day 1.

The primary endpoint is the number of participants with spontaneous reperfusion on Day 1. The registry defines spontaneous reperfusion using complete ST-segment resolution greater than 50% on a pre-PCI ECG, taken immediately before angiography. This is a binary outcome at the participant level: each participant either meets the specified endpoint definition or does not.

ECG evidence of ST-segment resolution is used in the endpoint as a marker of reperfusion before PCI. It allows the study to ask whether reperfusion is already apparent before the procedure, rather than relying only on measures collected after PCI. This gives the endpoint a temporal distinction from the listed secondary outcome of complete ST-segment resolution at 30 minutes post PCI. These two assessments refer to different points in the care pathway and should not be treated as interchangeable.

The endpoint description also says its population is patients who did not have a pre-PCI ECG. That wording is difficult to reconcile with an endpoint assessed by a pre-PCI ECG. The record does not explain the intended handling of this issue or specify how many participants were eligible for the primary analysis. Most importantly, the registry record does not report the number meeting the endpoint, the number assessed, or an estimate of uncertainty. The definition is available, but the endpoint result cannot be interpreted from the record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help connect a clinical question to an outcome definition, a population, and an analysis. For this study, the registry identifies a binary primary outcome: participants are counted according to whether they meet the definition of spontaneous reperfusion. The outcome is assessed using a pre-PCI ECG and a threshold of complete ST-segment resolution greater than 50%. The record names the timeframe as Day 1. These details define what the measure is intended to capture, but the record does not report the count used in an analysis.

What can a participant count tell us?

General statistical explanation: for a binary outcome, a count can be presented alongside the number of participants assessed. The count describes how many observed participants met the endpoint definition. A proportion can also summarize the frequency, but it needs a clear denominator: the number of participants with usable outcome data for the relevant analysis. The registry reports enrollment of 15, but does not report the number assessed for the primary endpoint or the endpoint count. Enrollment alone should not be assumed to equal the analysis denominator.

General statistical explanation: an estimate from a small study can be uncertain because each participant represents a substantial part of the observed group. A confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method. It does not account automatically for problems such as outcome misclassification, missing measurements, or selection into the analysis population. No primary endpoint confidence interval is reported in the registry record.

Why does the design matter for estimation?

This is a prospective single-group study, with no randomized control group. Descriptive statistics can characterize outcomes in participants who received the study approach and standard care. A treatment contrast, by contrast, requires a comparator and an analysis that estimates differences between groups. Without a concurrent control group, it is not possible to estimate a randomized between-group effect from this design. The registry lists allocation as not applicable and masking as none.

General statistical explanation: random allocation helps make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. A single-arm study does not gain that protection through randomization. Even when an outcome is observed after an intervention, its occurrence cannot be attributed to that intervention solely from the timing. The course of the condition, standard care, and participant-level factors can also contribute. This is why a single-arm endpoint count should be described as an observation, not as proof of a causal treatment effect.

How should planning assumptions be read?

The registry includes assumptions for a sample-size planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. This is identified as a planning illustration rather than the trial's own design. It does not describe the actual single-group enrollment plan, and it is not observed power. The illustration's numerical sample-size results are not reported in the registry record.

General statistical explanation: a sample-size calculation is a planning tool. It depends on assumptions about the outcome, target effect, variability or event frequency, significance level, power target, and analysis. When a planning scenario uses a fraction of an observed effect, the resulting estimate depends on the observed effect chosen as its reference. A planning estimate cannot recover a missing trial result and should not be presented as evidence that a study had a particular probability of detecting an effect after the data were collected. In a single-arm trial, an illustration based on equal allocation to two arms is also distinct from the registered design.

What do over-dispersion and model choice mean?

General statistical explanation: over-dispersion occurs when outcome variability is greater than a statistical model expects. It matters because a model that understates variability can produce confidence intervals that are too narrow and tests that are too optimistic. This concern often arises with count data, where observations may vary more than a simple model allows. The primary outcome in this study is described as a count of participants with a binary event, not as a repeated event rate. The registry record does not report a model, an over-dispersion assessment, or a model-based estimate for the primary outcome.

For a binary endpoint, an analysis might report the observed count and denominator, a proportion with an interval, or a comparison if an appropriate comparator exists. Which analysis is suitable depends on the protocol and the intended estimand. The registry does not report its statistical analysis plan, so the intended estimator, handling of covariates, confidence-interval method, and hypothesis test are not reported in the registry record. These details should not be inferred from the endpoint definition.

The registry lists nine outcome measures and zero analysis entries. That means the record contains outcome descriptions but no posted analysis results for interpretation. Neither the name of an endpoint nor a study's completed status supplies an estimate. Until outcome data and their analysis are reported, readers cannot judge the magnitude, precision, or statistical compatibility of the primary outcome.

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("Adult Patients With High Risk STEMI")
n      <- c(11)
events <- c(2)
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  Adult Patients With High Risk STEMI  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including a primary outcome and secondary outcomes relating to post-PCI ST-segment resolution, left ventricular ejection fraction, wall motion score index, and microvascular perfusion score index. It does not report how many hypotheses were intended for formal testing, whether any outcomes were designated for confirmatory inference, or how multiplicity was to be handled. A multiplicity plan is not reported in the registry record.

General statistical explanation: when several outcomes or hypotheses are examined, the chance of at least one apparently unusual result can increase if each is interpreted without regard to the others. Adjustment methods, hierarchical testing, or a clear distinction between confirmatory and exploratory outcomes can address this issue, depending on the research plan. No particular strategy should be assumed for this study. Since the registry contains no analysis results, there is also no basis for assessing the impact of multiplicity on reported findings.

The registry record does not report a missing-data method, the number of participants with missing ECG or echocardiographic measurements, or a primary analysis population. The endpoint description's reference to patients who did not have a pre-PCI ECG raises a question about endpoint evaluability, but the record does not explain how such participants were treated in the analysis. There is no information about imputation, complete-case analysis, or sensitivity analyses.

General statistical explanation: missing outcome data can affect interpretation when the availability of a measurement is related to participant condition or outcome status. Reporting the enrolled population, the population assessed for each endpoint, reasons for missingness, and the analysis method helps readers assess this risk. Those details are not reported in the registry record. An intention-to-treat population, per-protocol population, or other analysis set should not be presumed from the single-group design.

The registry also does not report an interim analysis plan or a statistical analysis plan. The absence of these details limits assessment of prespecification and analytic choices; it does not establish that such plans did not exist outside the registry.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ventricular fibrillation arrest during angiography (6.7%), lv thrombus displayed at discharge echocardiogram (6.7%), congestive heart failure due to severe mitral regurgitation (6.7%).

The safety record lists 15 participants at risk for serious adverse events and 3 participants affected. For other adverse events, it lists 15 at risk and 6 affected. The registry lists zero deaths. These are counts for the study group, not comparisons with a control group. The serious and other adverse event counts should not be added together because the record does not explain whether participants could appear in both categories.

The three serious adverse event terms listed are ventricular fibrillation arrest during angiography, LV thrombus displayed at discharge echocardiogram, and congestive heart failure due to severe mitral regurgitation. Each term is recorded as 6.7%. The registry does not report event-level details such as timing, duration, recurrence, severity grading beyond the serious classification, or whether an event was considered related to the intervention.

These entries are descriptive safety observations in a small single-group study. They do not determine whether the intervention caused an event, and without a comparator they do not estimate relative risk. The counts also do not establish that unlisted events did not occur; they describe the adverse event information included in the registry record. A causal safety assessment would require fuller clinical context and an appropriate comparative design or other evidence beyond these entries.

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

The registry record establishes that a prospective phase 2 single-group study of sonothrombolysis with Definity alongside standard care enrolled 15 participants and is marked completed. It defines spontaneous reperfusion using complete ST-segment resolution greater than 50% on a pre-PCI ECG immediately before angiography. It also records selected adverse event counts and lists several secondary outcome measures. These are meaningful descriptions of the study's scope and reporting.

They do not establish the primary outcome frequency. The number of participants with spontaneous reperfusion is not reported in the registry record, nor are the number assessed, an uncertainty interval, or a statistical test. The secondary outcome results are also not reported. Readers therefore cannot determine from this record how the enrolled group performed on the intended endpoints or how precisely outcomes were measured.

The design places a further boundary on interpretation. Because the study is single-group and has no randomized control arm, any recorded outcome would describe participants receiving sonothrombolysis with standard care. It could not, by itself, show what would have occurred under standard care alone or support a randomized treatment-effect estimate. Observed outcomes in a single group can reflect the intervention, the underlying condition, standard care, and other influences.

The safety counts likewise describe recorded events, not causal effects. The record lists serious adverse events affecting 3 participants, other adverse events affecting 6 participants, and zero deaths. No control group is available for comparison, and the registry does not state whether the events were attributed to the intervention. These data should be read as descriptive reporting rather than as a definitive assessment of comparative safety.

In short, the record supports an account of the study design, endpoint definition, enrollment, and selected safety information. It does not support a conclusion about the primary outcome or a causal claim about sonothrombolysis. The absence of reported outcome analyses is a limit on what can be inferred, not evidence that an outcome was favorable or unfavorable.

14. Why This Trial Matters Statistically

This study is statistically instructive because its clinical question and its design answer different kinds of questions. The primary endpoint asks how many participants show ECG evidence of spontaneous reperfusion before PCI. A single-group study can describe that frequency if the result and analysis denominator are reported. It cannot provide a randomized comparison with standard care alone because there is no control arm.

The endpoint timing also matters. Spontaneous reperfusion is assessed before PCI, while a listed secondary measure concerns ST-segment resolution after PCI. Separating measurements by their timing helps avoid treating pre-procedure and post-procedure outcomes as if they represented the same event or clinical stage. The registry provides the endpoint definitions and timeframes, but not the corresponding results.

The record also illustrates the difference between study registration and outcome reporting. A registry entry can identify an intended endpoint, enrollment, and safety information without presenting the data needed to estimate an outcome or its precision. In this case, the endpoint definition is specific, but the number meeting it and the analysis population are not reported. That distinction is central to transparent statistical interpretation.

Finally, planning illustrations should not be confused with what the trial actually tested. The registry describes a sample-size illustration based on two-arm assumptions even though the registered study is single-group. Such planning assumptions are not a substitute for the study's own design or a reported statistical analysis. No sample-size justification for the actual trial is reported in the registry record, and planning estimates are not observed power.

The statistical value of the record lies in clarifying what was intended to be measured and where interpretation stops. It lets readers identify the primary question, understand the absence of a randomized comparator, and recognize the need for endpoint results and analysis details before drawing conclusions about magnitude or precision.

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 most direct limitation is that the registry record does not report the primary endpoint result. It gives no count of participants meeting the spontaneous reperfusion definition, no denominator for the primary analysis, and no estimate of uncertainty. Secondary outcome results are not reported either. Without these results, the study's outcomes cannot be quantitatively interpreted from the registry record.

The study enrolled 15 participants and used a single-group design. The absence of a concurrent randomized comparator prevents a like-for-like estimate of treatment effect. The registry also lists no masking. These design features do not invalidate descriptive observations, but they limit causal interpretation and leave outcomes open to influences unrelated to the study intervention.

The endpoint population description is unclear: it refers to patients who did not have a pre-PCI ECG, while the endpoint itself is assessed using a pre-PCI ECG. The record does not explain this wording, report the number of participants with an evaluable ECG, or describe the handling of missing measurements. This makes it difficult to identify the intended analysis denominator.

Other details needed for statistical appraisal are not reported in the registry record, including the actual trial's sample-size justification, statistical analysis plan, multiplicity approach, analysis populations, and missing-data methods. The record lists nine outcome measures but no analysis entries. It also does not report whether any outcomes were examined at interim analyses. These omissions constrain assessment of prespecification and precision; they should not be treated as proof that plans or analyses did not exist elsewhere.

Safety findings are also limited to descriptive counts and selected terms. The registry does not provide a randomized safety comparison or establish attribution of events to the intervention. The reported counts therefore cannot be interpreted as causal risk estimates.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sonothrombolysis in Patients With STEMI — NCT03092089.
• Registry record last updated 2021-06-09; status last verified 2021-05.
• Results first posted 2021-06-09.
• 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

NCT03092089 is a completed prospective phase 2 single-group study titled Sonothrombolysis in Patients With STEMI. The registry reports enrollment of 15 and describes sonothrombolysis with Definity in addition to standard care with reperfusion therapy using PPCI. The primary endpoint is the number of participants with spontaneous reperfusion on Day 1, assessed by complete ST-segment resolution greater than 50% on a pre-PCI ECG immediately before angiography.

The registry record does not report the primary endpoint result, secondary outcome results, or analysis estimates. It lists serious adverse events affecting 3 of 15 participants, other adverse events affecting 6 of 15, and zero deaths. With no randomized comparator and no posted outcome analyses, the record supports description of the design and recorded safety counts, but not an estimate of comparative treatment effect.