An International Pulmonary Embolism Registry Using EKOS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An International Pulmonary Embolism Registry Using EKOS (NCT03426124), a registered phase not stated study. The primary outcome is Change in RV/LV Ratio on Echocardiogram (Matched Pairs as Available).

2. Clinical Question

The registry aims to describe acoustic pulse thrombolysis regimens used in routine care globally and the clinical outcomes of people who have received or will receive this treatment. It is not designed, as described in the record, as a randomized comparison of the device and thrombolytic regimen against another treatment. The central question is therefore descriptive: how the treatment was used and what outcomes were recorded in treated participants.

The endpoint focuses on a change in an imaging measurement rather than a direct comparison between treatment groups. Because the registry reports the primary outcome only for participants with matched echocardiograms, the question also concerns the subset for whom both measurements were available. How that subset relates to all enrolled participants is not reported in the registry record.

3. Trial Design

This is an international registry of treatment and clinical outcomes among people with pulmonary embolism. It is marked completed, with enrollment of 1480. The registry includes both retrospective and prospective participants treated with the EkoSonic Endovascular System and a thrombolytic drug. The record describes a registry intended to understand treatment regimens used as standard of care globally, rather than a randomized trial that assigns participants to competing interventions.

The retrospective group includes individuals with intermediate-high or high risk pulmonary embolism who were consecutively treated with the device and thrombolytic drug between January 2014 and one year prior to site activation. The prospective group includes individuals with intermediate-high or high risk pulmonary embolism for whom the treating investigator selected the device and thrombolytic drug. In that group, the duration of ultrasound and volume of thrombolytic drug were left to physician discretion. These descriptions indicate that treatment was selected in clinical practice, not allocated by a stated randomized procedure.

The two groups are not a like-for-like control comparison. They differ in how participants entered the registry and in the period of data collection. The record does not report a randomized allocation or a control arm. Consequently, a difference between retrospective and prospective observations would not, by itself, estimate a causal treatment effect. Participant characteristics, clinical decisions, data collection, and availability of measurements could all differ between the groups; details addressing those possibilities are not reported in the registry record.

The primary outcome is change in echocardiographic RV/LV ratio among participants with matched pre-procedure and post-procedure echocardiograms. The record defines the outcome as a mean with standard deviation and gives a timeframe extending from baseline to post-procedure, through discharge from the index hospitalization up to 14 days. Its outcome description also specifies a post-procedure echocardiogram 24-48 hours after therapy initiation. The numerical endpoint result and the statistical analysis used to produce it are not reported in the registry record.

The record lists 12 outcome measures and 0 analyses. The enrollment target and the number enrolled are represented in the registry record, but details of any sample-size justification for the registry are not reported in the registry record. The retrospective and prospective groups should be understood as registry cohorts, not experimental treatment arms intended to establish comparative efficacy.

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: Subjects with matched pairs (pre-procedure echocardiogram and post-procedure echocardiogram through discharge from index hospitalization) have been reported.

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 Change in RV/LV Ratio on Echocardiogram (Matched Pairs as Available), measured over Baseline to post-procedure (end of procedure through hospital discharge up to 14 days).

The primary endpoint is the percent change in the ratio of right ventricular to left ventricular diameters measured by echocardiogram. The RV/LV ratio is an imaging measure of the relative dimensions of the right and left ventricles. Measuring it at baseline and again after a procedure allows the registry to describe how this cardiac imaging measure changed over the specified observation period.

The endpoint is defined using matched pairs: a participant must have both a pre-procedure echocardiogram and a post-procedure echocardiogram to contribute to this outcome. The registry describes the post-procedure assessment as occurring 24-48 hours after therapy initiation, while its timeframe also allows post-procedure assessment through discharge from the index hospitalization up to 14 days. The exact timing for each participant and the handling of measurements taken at different times are not reported in the registry record.

Using a continuous measure retains information about the magnitude and direction of change rather than reducing the outcome to a binary category. Reporting a mean and standard deviation can describe the average change and the spread of individual observations. This is a general statistical explanation; the registry record does not provide the actual mean, standard deviation, confidence interval, or participant count for the primary endpoint. It is therefore not possible to assess the observed magnitude or precision from the endpoint definition alone.

The matched-measurement requirement is important to interpretation. Participants without both measurements do not contribute to the paired endpoint as described, and the registry record does not report how many participants had matched pairs or why other measurements were unavailable. The endpoint is an imaging outcome; it should not be treated as a direct substitute for every clinical outcome or as evidence of a treatment effect relative to an untreated or alternative-treatment group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, summarized in the registry description as a mean with standard deviation. In general, a mean describes the average observed value, while a standard deviation describes the spread of observations around that average. For a change endpoint, the mean would describe the average change among participants included in the analysis; the standard deviation would indicate how varied those changes were. Neither statistic is a measure of uncertainty in the mean by itself. A confidence interval, if reported, would describe a range of estimates compatible with the data under the chosen statistical model. No mean, standard deviation, or confidence interval for the primary outcome is reported in the registry record.

The paired structure means that the endpoint depends on measurements from the same participant at baseline and after treatment. In general, analyzing within-person changes can account for the fact that measurements from one participant are related, rather than treating the two measurements as independent observations. The registry identifies matched pairs as available but does not report the specific paired analysis method, the number of complete pairs, or the distribution of individual changes. It also does not report whether the percent change was calculated for each participant before averaging or by another approach. The detailed computational definition is therefore not available in the registry record.

The time window needs attention. The outcome title and timeframe describe baseline to post-procedure, with post-procedure observation through discharge from the index hospitalization up to 14 days. The outcome description states that the post-procedure echocardiogram was 24-48 hours after initiation of therapy. These descriptions identify the intended comparison but do not explain how scans at different times were handled, whether one time point was preferred, or how participants without a scan in a specified window were treated. Those details are not reported in the registry record.

The phrase “matched pairs as available” signals that the analysis population may be smaller than the full enrolled registry population. General statistical interpretation of a paired mean requires knowing how many participants contributed both measurements and whether their availability is related to outcomes or participant characteristics. If missingness is systematic, the observed mean can differ from the mean that would have been observed in the full cohort. This is a general limitation of incomplete repeated measurements. The registry record does not report missing-data methods, reasons for missing scans, or a comparison of participants with and without matched pairs.

Randomization and a control group are not described. In a randomized trial, allocation can help balance measured and unmeasured factors between treatment groups on average. A registry based on treatments selected in practice does not gain that protection simply by having retrospective and prospective cohorts. General comparisons across such groups can reflect differences in severity, selection, clinical decisions, follow-up, or recording as well as any treatment-related differences. The registry record describes consecutive retrospective inclusion and physician discretion in prospective treatment details, but it does not report an adjustment strategy for confounding or a comparative causal analysis.

The listed planning illustration has a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is a stated fraction of the observed effect. In general, such a calculation asks how many participants per arm might be needed under specified assumptions to detect a chosen effect with a given power. It is a planning illustration, not an observed power calculation and not evidence that the registry was designed or sized according to those assumptions. The registry record does not report a sample-size justification for its design. The numerical inputs and resulting planning estimates are not reported in the registry record.

Over-dispersion is a general issue when outcome variability is greater than a statistical model assumes. It can make standard errors too small if the extra variability is ignored, leading to confidence intervals that are too narrow and tests that appear more decisive than warranted. The primary endpoint is continuous and the record describes a standard deviation, but it does not report a model, a variance assumption, or an over-dispersion assessment. This concept should not be taken as a claim that over-dispersion was present in this registry.

Multiplicity refers generally to the increased chance of obtaining at least one apparently unusual result when many outcomes or tests are considered. The record lists 12 outcome measures, but no analyses are listed. It does not report an outcome hierarchy beyond identifying the primary endpoint, a multiplicity adjustment, or a plan for interpreting secondary outcomes. It is not possible to determine from the record whether any formal adjustment was intended or performed.

For the reported safety information, the registry provides counts in retrospective and prospective groups and lists selected serious-event terms with percentages. In general, counts depend on how events are defined, collected, and attributed, while percentages also depend on their denominators. The record does not explain whether participants could contribute more than one event, how event terms were coded, whether events were treatment-related, or what denominator was used for each percentage. Consequently, the safety figures should be interpreted as reported registry observations rather than comparative rates or estimates of causal risk.

Most importantly, no inferential results for the primary endpoint are reported in the registry record. There are no posted estimates from which to assess uncertainty, test results, model fit, or sensitivity to analytic choices. The methods description can explain how such statistics would generally be interpreted, but it cannot establish which methods were actually applied in the registry analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Retrospective", "Prospective")
n   <- c(276, 176)
m   <- c(-22.6, -22.6)
sp  <- c(20.8, 19.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Retrospective  276  -22.600  20.800  -25.065  -20.135
CARM  Prospective  176  -22.600  19.900  -25.560  -19.640

11. Multiplicity, Missing Data and Analysis Populations

The record identifies a primary endpoint and lists 12 outcome measures, but it lists 0 analyses. It does not report a statistical analysis plan, a hierarchy among secondary outcomes, or a method for adjusting for multiple comparisons. In general, testing many outcomes can increase the chance of at least one apparently notable finding by chance. An adjustment can address that issue, but the registry record does not say whether one was planned or used. Since numerical analyses are not reported, multiplicity cannot be evaluated from the posted results.

The primary outcome is defined only for participants with matched baseline and post-procedure echocardiograms. That makes the analysis population a subset determined by measurement availability. The number with matched pairs and the number excluded from this endpoint are not reported in the registry record. Reasons for missing echocardiograms, missing-data assumptions, imputation methods, and sensitivity analyses are also not reported in the registry record.

As a general matter, missing outcome measurements can affect interpretation if they are related to participant condition, treatment course, or other factors associated with the outcome. A matched-pair analysis describes people with both scans; it does not automatically describe all enrolled participants. Without information on missingness and the analytic population, readers cannot judge the extent to which the reported endpoint, if available, would represent the full registry cohort.

The record does not report how the primary endpoint population relates to the retrospective and prospective cohorts, or whether any subgroup analyses were planned. It also does not report an analysis population definition for the other outcomes. These omissions limit assessment of selective availability, multiplicity, and the scope of any outcome conclusions.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (1.4%), death (1.0%), cardiac arrest (1.0%), haematoma (0.7%), deep vein thrombosis (0.5%).

The registry reports serious adverse event counts in both groups: 100 affected among 991 at risk in the retrospective group, and 39 affected among 489 at risk in the prospective group. It also reports other adverse event counts: 63 affected among 991 at risk retrospectively and 40 among 489 at risk prospectively. Death counts are 50 in the retrospective group and 15 in the prospective group. These are registry counts, not estimates from a randomized comparison.

The most frequently listed serious-event terms include Pulmonary embolism at 1.4%, Death at 1.0%, Cardiac arrest at 1.0%, Haematoma at 0.7%, Deep vein thrombosis at 0.5%, and Gastrointestinal haemorrhage at 0.5%. The denominators for these percentages and whether a participant could appear under more than one term are not reported in the registry record. The figures should not be summed or treated as mutually exclusive categories.

These counts do not establish whether events were caused by the device, thrombolytic drug, underlying pulmonary embolism, or other factors. Definitions, collection procedures, event timing, and attribution are not reported in the registry record. The groups also are not a like-for-like control comparison. Differences in their counts cannot by themselves show a comparative safety effect. They describe recorded events in the registry cohorts, with the limitations of observational reporting and unreported event detail.

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

The registry is relevant as a description of an international experience with the EkoSonic Endovascular System and thrombolytic treatment in intermediate-high or high risk pulmonary embolism. It includes retrospective and prospective records and identifies a clinically interpretable imaging outcome: change in RV/LV ratio on echocardiogram. Its design can provide context about treatment use and recorded outcomes in practice, when those results are reported with sufficient detail.

The registry record does not report the numerical primary endpoint result. It therefore does not show the observed average percent change, the variation among participants, or the precision of an estimate. Without those values, the endpoint definition alone cannot establish the size, direction, or consistency of any change. The record also does not report a primary endpoint confidence interval or p-value.

The design does not support a direct causal comparison between the retrospective and prospective groups. The groups were assembled differently, treatment details were selected in clinical practice, and no randomized control arm is described. Any differences between group observations could reflect differences in participants, treatment decisions, follow-up, or record completeness. The record does not report an adjustment strategy that would resolve these concerns.

The safety information is also descriptive. It gives event counts by registry group and selected serious-event terms with percentages, but does not supply event attribution, detailed definitions, or percentage denominators. Such counts do not prove that treatment caused the events, nor do they provide a controlled comparison with another approach.

In general, an estimate is more useful when its population, measurement timing, missing-data handling, and uncertainty are clear. Those details are not fully reported for this primary endpoint. The registry can be read as a framework for collecting routine-care experience, but the posted record does not permit conclusions about comparative benefit, causal effects, or the precision of the primary outcome. Any interpretation should remain within those descriptive limits.

14. Why This Trial Matters Statistically

This registry illustrates a common statistical challenge in clinical research: measuring outcomes in routine practice while treatment decisions remain with clinicians. That design can capture experience outside a tightly controlled experiment, including retrospective cases and prospective treatment use. It also means that observed outcomes arise in a setting where treatment selection, follow-up, and documentation may vary. Statistical interpretation must distinguish descriptive evidence from a controlled estimate of treatment effect.

The primary endpoint makes the measurement structure especially important. It is defined as a change in echocardiographic RV/LV ratio and requires matched measurements. A result based on participants with both scans may not automatically generalize to every enrolled participant. The number of matched pairs, missing-data handling, and timing details are essential to understanding what population an estimate represents, but are not reported in the registry record.

The registry also emphasizes why an endpoint definition is not the same as an endpoint result. The record identifies what was to be measured and gives a mean and standard deviation as the summary approach, yet the numerical outcome is not reported. Without an estimate and a measure of precision, readers cannot judge whether the observed change was small or large, consistent or variable, or estimated narrowly or imprecisely.

Finally, the registry groups should not be mistaken for a randomized treatment comparison. The retrospective and prospective cohorts differ in their sources and treatment selection, and no control arm is described. Recognizing this distinction prevents descriptive counts from being read as causal evidence. The case is statistically important because it shows how design, endpoint completeness, event reporting, and analysis transparency shape what conclusions an observational registry can support.

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 consequential limitation is that the primary endpoint result is not reported in the registry record. Although the outcome is defined as mean percent change in RV/LV ratio with standard deviation, neither the estimate nor its precision is available. The record also does not give the number of participants contributing matched echocardiograms. This prevents assessment of the size and reliability of the primary outcome.

Measurement timing is described both as 24-48 hours after therapy initiation and as post-procedure through discharge from the index hospitalization up to 14 days. The record does not explain how measurements at different times were handled or whether a single post-procedure time point was selected for analysis. Variation in timing could matter when interpreting a change measured over time; the record does not provide enough detail to assess it.

The registry is observational and does not describe randomized allocation or a control arm. The retrospective and prospective cohorts differ in how participants entered the registry, and prospective treatment duration and drug volume were left to physician discretion. Consequently, the cohorts are not interchangeable controls. Adjustment for participant differences, confounding, and treatment selection is not reported in the registry record.

The endpoint requires matched measurements, but the record does not report missingness, reasons for unavailable echocardiograms, or methods for handling missing data. The listed 12 outcome measures and 0 analyses leave multiplicity procedures and analysis populations unclear. Safety reporting is limited by unreported event definitions, attribution, timing, and percentage denominators. These limitations restrict both the interpretability of individual results and the strength of conclusions that can be drawn from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An International Pulmonary Embolism Registry Using EKOS — NCT03426124.
• Registry record last updated 2023-02-22; status last verified 2022-05.
• Results first posted 2023-02-22.
• 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

NCT03426124 is a completed international registry of the EkoSonic Endovascular System with thrombolytic treatment for pulmonary embolism. Enrollment is 1480. It includes retrospective and prospective cohorts of people with intermediate-high or high risk pulmonary embolism; the prospective treatment details were selected at physician discretion.

The primary endpoint is mean percent change in echocardiographic RV/LV ratio among participants with matched baseline and post-procedure measurements. The registry lists 12 outcome measures and 0 analyses. The numerical primary outcome and its precision are not reported in the registry record.

Safety counts and selected serious-event percentages are reported, but event attribution and percentage denominators are not reported. The cohorts are not a randomized comparison or like-for-like control groups, so the registry supports descriptive interpretation rather than a direct causal treatment comparison.