Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia (NCT02919618), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Reduction in Ventricular Tachycardia (VT) Burden.

2. Clinical Question

3. Trial Design

This was a completed Phase I/II, single-group study sponsored by Washington University School of Medicine. The registry record lists enrollment of 19, allocation as not applicable, and masking as none. There was no randomized or concurrent control arm. Consequently, the study design does not support a like-for-like comparison between treated participants and an untreated group.

The intervention was stereotactic body radiotherapy (SBRT), delivered noninvasively in a single fraction. The treatment region was determined by EP guidance using noninvasive electrical mapping combined with anatomic imaging. The primary efficacy endpoint compared ventricular tachycardia burden during the six months before treatment with burden during the six months after treatment. The timeframe is described as 12 months, and the endpoint description specifies a six-week blanking period after therapy to allow for an ablation effect. For participants with PVC-induced cardiomyopathy, the endpoint was any reduction in PVC burden based on ambulatory heart monitors.

The record lists a study start of 2016-07 and primary completion of 2018-07-23, with status recorded as completed. It lists nine outcome measures, including overall survival, adverse events possibly, probably or definitely related to treatment, health-related quality of life, reductions in VT burden, ICD shocks and VT therapies, and LVEF improvement. These are listed outcomes, not evidence that each outcome was analyzed or that results were posted.

The record does not report the protocol’s statistical plan, sample-size justification, interim analyses, or detailed analysis populations. It also does not report a randomized comparison. The pre-treatment period offers a within-person reference, but time-related changes and other differences between periods cannot be separated from a treatment effect using a concurrent control comparison.

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: Nineteen patients were consented, screened, and deemed eligible for SBRT. Two additional patients signed consent and went through screening procedures; however, were later deemed ineligible to obtain SBRT.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis is based on number of SAE events that occurred in 19 participants within 90 days after SBRT.

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 Reduction in Ventricular Tachycardia (VT) Burden, measured over 12 months (6mo prior to and 6mo post SBRT).

The primary endpoint counts participants with a reduction in ventricular tachycardia (VT) burden. For participants assessed through ICD monitoring, the endpoint compares VT events in the six months before SBRT with events in the six months after SBRT. The description includes ATP and ICD shocks, as well as sustained, untreated slow VT. A six-week blanking period after therapy was specified to allow for an ablation effect. For patients with PVC-induced cardiomyopathy, the primary efficacy measure was any reduction in PVC burden based on ambulatory heart monitors.

This endpoint is used to describe whether participants’ arrhythmia burden changed across the specified periods. Continuous ICD monitoring can capture device-treated episodes and the specified untreated slow VT; ambulatory heart monitors are the stated method for assessing PVC burden in the relevant patients. Counting participants with a reduction gives a participant-level summary rather than a measure of the size of each person’s change.

The endpoint definition does not state a minimum reduction threshold for the primary outcome. The record separately lists secondary outcomes with thresholds of 50% and 95% reduction in VT burden, but those thresholds should not be substituted for the primary endpoint. The primary outcome is described, but the number of participants meeting it and an estimate of uncertainty are not reported in the registry record. The record also does not provide details on how the different monitoring measures were combined or how an individual reduction was classified.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count measure?

The primary endpoint is a count of participants meeting a reduction criterion, rather than a count of VT episodes or a mean change in episode burden. In general, a participant-level count can be easy to interpret as a summary of how many people experienced the defined outcome. It also compresses information: participants with small and large reductions may both be counted as having a reduction. The record does not report the primary count or the rule used to classify a participant as having a reduction, beyond the description of the monitoring periods and measures.

How does a before-and-after comparison differ from a control comparison?

In general, a before-and-after design compares observations from one group at different times. It can document temporal change within the study group, but it does not provide the same information as a concurrent control group, which can help distinguish changes associated with treatment from changes that might also occur without it. Here, the primary endpoint compares the six months before treatment with the six months after treatment, with a six-week blanking period after therapy. The registry record lists a single-group model and no allocation to separate arms. It does not report an analysis that adjusts for time-related influences or other potential differences between the periods.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure. It communicates uncertainty in a way that a single point estimate cannot. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone establishes that a result is clinically important. No primary efficacy estimate or confidence interval is reported in the registry record, so the precision of the primary outcome cannot be assessed from the posted results.

What would a p-value address?

In general, a p-value describes how compatible data are with a specified null hypothesis under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The registry record lists zero statistical analyses and does not report a primary p-value. The design also lacks a concurrent control group, so a p-value from a within-group before-and-after analysis would answer a different question from a randomized comparison.

Why do event counts and participant counts differ?

In general, an event count can include multiple events experienced by one participant, whereas a participant count records whether each person experienced at least one event or met a criterion. The primary outcome is explicitly a count of participants with a reduction, while its monitoring measures include device therapies and VT episodes. The record does not give a primary event total or the participant-level result. Safety figures likewise include participants at risk and participants affected; they are not interchangeable with the number of individual adverse-event episodes.

What do the planning illustrations represent?

The registry record describes planning illustrations computed from an observed effect, rather than from the trial’s own design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; for other illustrations, it is participants per arm. These assumptions describe hypothetical planning calculations, not the single-group study’s actual design. Such calculations are not observed power, and they do not show that the original study was planned with those assumptions. The record does not report the original sample-size justification. It also does not report the primary observed effect needed to interpret any planning illustration as a trial-specific target.

What is not established by the record?

The registry record does not report a statistical analysis plan, interim analyses, or detailed missing-data methods. It does not report primary efficacy results, uncertainty intervals, or p-values. In general, missing observations can affect an estimate if the participants with available measurements differ from those without them; assessing that possibility requires information about follow-up and missingness. The primary endpoint population description says that patients alive at 6 months were evaluated, but does not provide further details on the handling of participants without evaluable monitoring. No additional assumptions about those methods can be made from the registry record.

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("Patients With ICD-treated VT Indication", "Patients With PVC-Related Cardiomyopathy Indicatio")
n      <- c(16, 2)
events <- c(15, 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  Patients With ICD-treated VT Indication  16  15  93.8  69.8  99.8  71.7  98.9  71.3  98.5
ARM  Patients With PVC-Related Cardiomyopathy Indicatio  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The record lists nine outcome measures, covering survival, adverse events, health-related quality of life, VT burden, ICD shocks, LVEF improvement, and VT therapies. It reports zero statistical analyses. The presence of several outcomes raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that possibility. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a statistical plan specifying which comparisons were primary for inference. It is therefore not possible to determine how multiplicity was handled.

The primary endpoint description states that patients who were alive at 6 months were evaluated by comparing ICD treatments or PVC burden in the periods before and after SBRT. This defines an aspect of the population assessed, but the registry record does not give the number with evaluable measurements, the number excluded from the endpoint, or the handling of missing monitoring data. It does not report a missing-data method or sensitivity analysis. In general, missing observations can affect a result when availability of measurements is related to participants’ outcomes, but the record does not provide enough information to assess that possibility.

The record also does not describe analysis populations in detail, such as how participants were classified for each outcome or whether any participants were excluded from a particular analysis. The endpoint’s alive-at-6-months wording should not be extended into assumptions about other outcomes. Without these details and without posted efficacy analyses, readers cannot evaluate whether the reported population or missingness could alter the primary result.

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 tachycardia (47.4%), heart failure (31.6%), cardiac arrest (15.8%), hypotension (15.8%), acute kidney injury (10.5%).

For the overall group that received SBRT, the registry record lists 19 participants at risk for serious adverse events and 15 affected. For other adverse events, it lists 19 at risk and 19 affected. The record also lists 8 deaths. These are counts for the study group; the information does not provide a concurrent control group or a comparative risk estimate.

The listed serious adverse-event terms and percentages are Ventricular Tachycardia, 47.4%; Heart Failure, 31.6%; Cardiac Arrest, 15.8%; Hypotension, 15.8%; Acute Kidney Injury, 10.5%; and Dyspnea, 10.5%. These percentages describe the registry’s reported terms. They should not be added together: the record does not say that the categories are mutually exclusive, and a participant may be represented under more than one term. The list does not establish that an event was caused by SBRT.

The outcomes list includes the number of adverse events possibly, probably or definitely related to study treatment, but a result for that outcome is not reported in the registry record. The record also does not provide event timing, duration, severity details beyond the serious classification, or causal attribution for the listed terms and deaths. Accordingly, the counts describe reported safety observations in this study, not a treatment-versus-control comparison or a causal estimate.

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

The registry record establishes that a Phase I/II study of EP-guided noninvasive cardiac SBRT was completed and enrolled 19 participants. It describes a single-fraction treatment directed to a heart region identified with noninvasive electrical mapping and anatomic imaging. Its primary efficacy endpoint was a participant-level reduction in VT burden, assessed by comparing six months before and six months after treatment, with a six-week blanking period after therapy. For patients with PVC-induced cardiomyopathy, the endpoint description instead specifies reduction in PVC burden measured with ambulatory heart monitors.

Those design details define what the study set out to assess; they do not establish the result. The number of participants with a primary endpoint reduction, an effect estimate, and a measure of uncertainty are not reported in the registry record. There are no reported statistical analyses. As a result, the size, precision and statistical significance of the primary efficacy comparison cannot be determined from the posted results.

The design also limits interpretation of any before-and-after change. Without a concurrent control group, a change over time cannot be attributed to treatment on the basis of this comparison alone. The study does not provide a like-for-like randomized comparison with which to estimate a relative treatment effect.

The safety counts indicate that serious and other adverse events were recorded in the treated group, and the record lists deaths and serious-event terms. They do not show how those counts compare with what would have occurred without treatment, and the registry record does not report the result for adverse events classified as possibly, probably or definitely related to treatment. These data should be understood as safety observations, not as proof of causation.

Overall, the registry record offers a description of the intervention, endpoint, design and posted safety counts. It does not provide the primary efficacy result or enough analysis detail to support a quantitative conclusion about efficacy or comparative safety.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a specialized, single-group clinical investigation frames an endpoint around repeated measurements in the same participants. The primary question compares VT burden before and after treatment, and the endpoint description identifies continuous ICD monitoring as the source for ATP, ICD shocks and sustained untreated slow VT. It also specifies ambulatory heart monitors for PVC burden in patients with PVC-induced cardiomyopathy. The distinct measurement approaches make it important to understand exactly which population and outcome are being summarized.

The design also illustrates the difference between a within-person reference period and a control arm. Pre-treatment observations provide context for post-treatment observations, but the study has no concurrent comparator. This affects the causal interpretation of any change and should be considered separately from the quality of the measurement itself.

The registry record’s separation of outcome listings from statistical analyses is important for evidence appraisal. Nine outcomes are listed, but zero analyses are reported, and the primary efficacy result is not reported in the registry record. Naming an endpoint does not supply an estimate, its precision, or the methods used to analyze it. This makes the distinction between a stated research question and a reported statistical result especially clear.

The safety information similarly demonstrates why counts require context. The record reports participants at risk and affected, serious-event terms and deaths, but does not provide a control group or a result for the listed treatment-related adverse-event outcome. These observations can describe what was recorded in the study, while leaving comparative and causal questions unresolved.

Finally, planning illustrations based on an observed effect should not be confused with the study’s original sample-size design or with observed power. Their stated hypothetical assumptions differ from the single-group design. The record does not report the original sample-size justification, so those planning assumptions cannot be used to reconstruct it.

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 main limitation for interpreting efficacy is that the primary endpoint result is not reported in the registry record. The endpoint is defined, but the number of participants with a reduction, effect estimate, confidence interval and p-value are absent. The record lists zero statistical analyses, so the posted information does not permit assessment of the magnitude or precision of the primary efficacy finding.

The study is single-group, with allocation listed as not applicable and masking as none. There is no concurrent control group for distinguishing a treatment-associated change from changes that could occur over time. The comparison of the six months before treatment with the six months after treatment is a within-person temporal comparison, not a randomized treatment comparison.

The endpoint description covers different monitoring measures and populations: ICD monitoring for VT and ambulatory heart monitors for PVC burden among patients with PVC-induced cardiomyopathy. The registry record does not report how many participants contributed data to each measure or how the endpoint was classified for each participant. It also does not report detailed eligibility criteria, participant characteristics, follow-up completeness, or missing-data methods.

The safety record lists counts and serious-event terms, but does not provide a control group, event timing, or causal attribution for the listed terms and deaths. A result for adverse events possibly, probably or definitely related to treatment is not reported in the registry record. These gaps limit interpretation of comparative safety as well as efficacy.

The record does not report the original sample-size justification, statistical analysis plan, interim analyses, multiplicity approach, or detailed analysis populations. These omissions prevent readers from assessing those aspects of the study’s planned and conducted analyses. No assumptions about unreported methods or results can resolve these limitations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia — NCT02919618.
• Registry record last updated 2024-08-21; status last verified 2024-07.
• Results first posted 2019-09-10.
• 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 NCT02919618, a completed Phase I/II study of EP-guided noninvasive cardiac radioablation for ventricular tachycardia. Washington University School of Medicine is listed as sponsor. Enrollment was 19; the study was single-group, with allocation not applicable and no masking. The intervention was a single fraction of noninvasive SBRT directed to a heart region determined with noninvasive electrical mapping and anatomic imaging.

The primary endpoint compared VT burden in the six months before and after treatment, with a six-week blanking period. For patients with PVC-induced cardiomyopathy, the endpoint description used PVC burden measured by ambulatory heart monitors. The registry record lists nine outcome measures, including safety, survival, quality of life and arrhythmia outcomes, but reports zero statistical analyses and does not report the primary efficacy result.

Safety counts include 15 of 19 participants affected by serious adverse events, 19 of 19 affected by other adverse events, and 8 deaths. The record does not establish causal attribution or provide a control-group comparison.