A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE) (NCT04524364), a na na study. The primary outcome is Number of Participants With Primary Adverse Events (PAEs).

2. Clinical Question

The study asks whether a pulsed field ablation system using irreversible electroporation can be used to isolate the pulmonary veins in participants with paroxysmal atrial fibrillation, with safety and long-term effectiveness as its stated objectives. The primary endpoint concerns the occurrence of specified primary adverse events during the period after the procedure.

The registry also lists outcomes concerning acute procedural success, freedom from documented symptomatic atrial arrhythmia recurrence from Day 91 to Day 365, and change in AFEQT total score. Those outcomes address procedural and longer-term questions distinct from the early safety endpoint. The posted information does not give an explicit primary-endpoint result or a comparative estimate against another treatment.

3. Trial Design

This is a completed, single-group device study sponsored by Biosense Webster, Inc. The registry lists an enrollment of 272 and identifies atrial fibrillation as the condition. The study began on 2020-08-23, and primary completion was recorded on 2023-05-09. The phase is listed as NA. Allocation is listed as NA, and masking is listed as NONE.

The intervention is pulsed field ablation therapy. The study description identifies an irreversible electroporation system consisting of a circular IRE catheter and an IRE generator, used for isolation of the atrial pulmonary veins. Eligible participants are described as having paroxysmal atrial fibrillation and being candidates for catheter ablation. There is no separate control arm described, so the design does not provide a randomized comparison with another procedure, device, or usual-care group.

The registry distinguishes Wave I, Wave II main phase, and Wave II roll-in participants. For the full analysis set in Wave I and Wave II main phase, the record says participants had to be enrolled and have insertion of the study catheter, with or without delivery of pulsed field ablation. The description of the Wave II roll-in analysis set is incomplete in the registry record, so its full membership definition is not reported in the registry record.

The stated primary objective is to demonstrate safety and long-term effectiveness. Five outcome measures are listed, including the primary safety outcome and secondary outcomes for acute procedural success, post-procedure arrhythmia freedom, and AFEQT score change. The record lists no analyses. Details of the statistical analysis plan, including any adjustment strategy or prespecified methods for the secondary outcomes, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Wave I and Wave II (Main Phase): The full analysis set (FAS) included all enrolled Wave I and Wave II (main phase) participants who had insertion of the study catheter (with or without delivery of pulse field ablation \[PFA\]); Wave II (Roll-in): The Roll-In analysis set (RI AS) included all Wave II (roll-in) participants who were enrolled in the roll-in phase and underwent ablation with the irreversible electroporation (IRE) ablation system.

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: Baseline characteristics were based on the full analysis set (FAS) for Wave I and Wave II (main phase) arms and the roll-in analysis set (RI AS) for the Wave II (roll-in) arm. FAS included all enrolled Wave I and Wave II (main phase) participants who had insertion of the study catheter (with or without delivery of PFA). The RI AS included all Wave II (roll-in) participants who were enrolled in the roll-in phase and underwent ablation with the irreversible electroporation (IRE) ablation system.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Primary Adverse Events (PAEs), measured over Within 7 days post-procedure on Day 0.

The primary endpoint is the number of participants with primary adverse events, measured within 7 days after the procedure on Day 0. The description defines the primary safety endpoint as the incidence of these events within 7 days of the initial mapping and ablation procedure. Its specified events include atrio-esophageal fistula; cardiac tamponade or perforation; device- or procedure-related death; major vascular access complication or bleeding; myocardial infarction; pericarditis; permanent phrenic nerve paralysis; pulmonary vein stenosis; stroke or cerebrovascular accident; thromboembolism; and transient ischemic attack.

This kind of endpoint is used to describe how often clinically important safety events occur during a defined period after a procedure. The event list and timeframe give the outcome a specific meaning: a count for this endpoint is not automatically interchangeable with a count of all adverse events or all serious adverse events. The registry record does not provide an explicit result for this primary endpoint, so the listed serious adverse-event summaries cannot establish the endpoint-specific count without confirmation that the event definitions and observation window match.

As a general statistical point, a count of participants with at least one qualifying event is a binary-outcome summary at the participant level: each participant either meets the endpoint definition during the stated period or does not. The event count alone does not describe the severity, timing, or recurrence pattern of events unless those details are also reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome type. The primary endpoint is a count of participants who experience at least one event meeting the endpoint definition. In general, this is analyzed as a binary outcome at the participant level. The numerator is the number who meet the definition, and the denominator is the number assessed in the relevant analysis population. The registry record gives the endpoint definition but does not report an explicit endpoint result or a corresponding uncertainty interval.

Why the event definition matters. The endpoint includes a specified list of events and a specified follow-up window. A general safety summary may use a broader definition, include a different period, or classify events differently. Consequently, an overall serious adverse-event count cannot be treated as the primary endpoint count unless the definitions, observation window, and analysis population align. The registry record does not state enough to confirm that alignment for the displayed serious-event summaries.

Single-group interpretation. In a single-group study, an event proportion describes what was observed among participants in the study under the stated conditions. It does not estimate a between-group contrast. A comparative interpretation would require a suitable comparator and an analysis designed to account for the study design. Neither a randomized allocation nor a control group is described in this record. As a general principle, comparisons with external rates can be misleading when populations, definitions, follow-up, and event ascertainment differ; no external comparison is reported.

Analysis populations. The record describes a full analysis set for Wave I and Wave II main phase that includes enrolled participants with insertion of the study catheter, with or without delivery of pulsed field ablation. It also identifies a separate roll-in analysis set, but the available description of that set is incomplete. Analysis-population definitions matter because the count and denominator may change depending on whether the analysis includes all enrolled participants, those who underwent catheter insertion, or those who received the procedure. The precise population used for each reported adverse-event summary is not fully explained in the registry record.

Uncertainty and confidence intervals. General statistical explanation: an estimate based on a limited number of observations has sampling uncertainty. A confidence interval communicates that uncertainty in the context of a specified statistical procedure. For a binary event outcome, an interval around an event proportion can show how compatible the data are with a range of underlying event rates. It is not a guarantee that the true value lies inside the interval, and it does not resolve possible bias from incomplete follow-up, outcome misclassification, or selection into the analysis population. The registry record does not report a confidence interval for the primary endpoint.

Event counts and over-dispersion. General statistical explanation: when outcomes are counts of events rather than participants with any event, a basic count model may assume that the variability follows a particular relationship to the mean. Over-dispersion means the observed variability is greater than that model assumes, and can make standard errors too small if not addressed. That issue is relevant when modeling repeated or recurrent events, but the primary endpoint is defined as the number of participants with primary adverse events, not a recurrent-event rate. The registry record does not report a model for recurrent events or an over-dispersion assessment.

Time-to-event outcomes. The listed secondary arrhythmia outcome uses Kaplan-Meier estimates of freedom from documented symptomatic recurrence from Day 91 to Day 365 after the index procedure. In general, Kaplan-Meier methods account for differing follow-up by using the observed time to an event or censoring. The resulting curve depends on assumptions about censoring and on consistent event ascertainment. The registry record names this outcome but does not report its estimate, confidence interval, censoring details, or analysis methods beyond the Kaplan-Meier reference.

Planning illustrations. The planning illustrations are not a description of the trial's own design or an observed-power calculation. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses the total number of events under a Schoenfeld approach; for other outcomes, it uses participants per arm. These assumptions describe hypothetical planning scenarios. They do not turn this single-group study into a two-arm comparison, and they do not establish a prespecified sample-size justification. The trial's sample-size justification is not reported in the registry record.

Multiplicity and statistical plan. Multiple outcomes create the possibility of interpreting chance findings as if they were definitive, particularly when many tests are made. General methods include prespecifying a primary outcome, controlling the family-wise error rate, or treating secondary outcomes as exploratory. The registry identifies a primary safety endpoint and lists secondary outcomes, but the analysis plan, testing hierarchy, and multiplicity procedures are not reported in the registry record. The registry lists no analyses, so there is no documented set of test statistics or model estimates to interpret.

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("Wave I", "Wave II: Main Phase", "Wave II: Roll-In")
n      <- c(40, 186, 30)
events <- c(0, 0, 0)
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  Wave I  40  0  0.0  0.0  8.8  0.0  8.8  0.1  8.6
ARM  Wave II: Main Phase  186  0  0.0  0.0  2.0  0.0  2.0  0.0  2.0
ARM  Wave II: Roll-In  30  0  0.0  0.0  11.6  0.0  11.4  0.1  11.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, with a primary safety endpoint and secondary outcomes that include acute procedural success, arrhythmia freedom, and change in AFEQT total score. It does not report a statistical analysis plan, a testing hierarchy, or a method for handling multiplicity. When a study assesses several outcomes, unadjusted tests can increase the chance of a chance-positive result across the set. Whether adjustment is needed depends on the study's aims and prespecified analysis strategy; that strategy is not reported in the registry record.

The record lists zero analyses. It therefore does not give outcome-specific estimates, uncertainty intervals, or statistical tests for the outcomes named. The absence of reported analyses does not establish that no analyses were performed; it means that the registry record does not report them.

Missing-data handling is not reported in the registry record. In general, missing outcome observations can affect both the denominator and the interpretation of an event rate or change score. The impact depends on why observations are missing, how much information is unavailable, and whether the analysis makes assumptions about those missing observations. The record does not specify follow-up completeness, imputation methods, censoring rules, or sensitivity analyses.

The registry describes a full analysis set for Wave I and Wave II main phase based on enrollment and catheter insertion, with or without pulse field ablation delivery. It identifies a Wave II roll-in analysis set but does not fully describe its membership in the available record. The precise analysis population for each adverse-event summary and each listed outcome is not reported in the registry record. These omissions limit assessment of whether the results include all relevant participants and whether comparisons across outcomes use consistent denominators.

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: atrial flutter (3.3%), respiratory tract infection (3.3%), nephrolithiasis (3.3%), acute coronary syndrome (2.5%), coronary artery occlusion (2.5%).

The adverse-event summary separates Wave I, Wave II main phase, and Wave II roll-in. For serious adverse events, it reports 3 of 40 for Wave I, 9 of 186 for Wave II main phase, and 2 of 30 for Wave II roll-in. For other adverse events, it reports 30 of 40, 85 of 186, and 17 of 30, respectively. Deaths are reported as 0 in each group. These are group-specific registry figures and should not be combined into a single total.

The summary also lists serious-event terms with registry-reported percentages: atrial flutter, respiratory tract infection, and nephrolithiasis at 3.3% each; acute coronary syndrome, coronary artery occlusion, and arthritis at 2.5% each. The record does not give the event counts or denominator underlying each term percentage in this summary, nor does it say whether participants could contribute more than one term.

These serious-event figures should not be assumed to be the primary adverse-event endpoint result. That endpoint has a specified event list and a 7-day window after the initial mapping and ablation procedure. The adverse-event summary does not establish that its definitions and timeframe are identical. It is descriptive safety information, not a comparative analysis.

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

The record describes a study of pulsed field ablation using an irreversible electroporation system in participants with paroxysmal atrial fibrillation. It specifies the primary safety endpoint and its follow-up window, identifies secondary outcomes, and reports group-level serious and other adverse-event summaries. These details help readers understand what the study intended to assess and what safety information the registry records.

The record does not provide an explicit result for the primary endpoint, a confidence interval for that endpoint, or analyses of the listed secondary outcomes. The serious adverse-event summaries do not automatically answer the primary endpoint question because the endpoint has a defined event list and observation window. The registry does not establish that the summaries use exactly those definitions and that same period.

Because the design is single-group, it cannot directly estimate how outcomes would differ under another treatment or procedure. No randomized comparator is described. Even a clearly reported event rate in this study would describe the observed participants, not prove that the device or procedure caused an outcome or that outcomes would be the same in other settings.

The listed secondary outcomes address acute procedural success, symptomatic recurrence of atrial arrhythmia after the initial post-procedure period, and quality of life measured with AFEQT. Their inclusion does not mean that results for those outcomes are available in the registry record. The record lists no analyses and does not report the methods used to handle missing data or multiple outcomes.

Accordingly, the strongest reading is descriptive: the registry documents the study framework, endpoint definitions, and adverse-event summaries, while leaving important result and analysis details unreported. It does not support a comparative effectiveness conclusion, and it does not provide enough information to quantify the primary safety endpoint with its precision.

14. Why This Trial Matters Statistically

This study is statistically notable because it brings together a device-based procedural intervention, a prespecified early safety endpoint, and outcomes intended to address both procedural performance and later experience. The primary endpoint focuses on specified adverse events during a defined period after the procedure. That specificity is important: safety interpretation depends on knowing which events count, when they are assessed, and which participants contribute to the denominator.

The study's single-group design also illustrates a central distinction between describing outcomes and estimating comparative effects. An event count can characterize what was recorded among study participants, but without a control group it cannot establish how those outcomes compare with another approach. A reader must avoid treating group labels such as study waves as if they were randomized treatment arms.

Separating the roll-in group from the main-phase groups is relevant to interpretation because analysis populations may differ. The registry gives a partial population definition for the main-phase full analysis set but does not fully describe the roll-in set in the available record. Clear population definitions and consistent follow-up are important for understanding denominators, missingness, and the applicability of any result.

The record also illustrates why outcome names and safety summaries are not substitutes for a reported analysis. The primary endpoint's specified events and time window may not match a broad serious adverse-event summary. The absence of an explicit endpoint result, uncertainty interval, and statistical analysis details limits what can be concluded from the registry record. Those are not merely technical omissions: they affect whether readers can assess the magnitude and precision of safety findings.

Finally, planning calculations should be kept separate from observed trial results. The stated planning assumptions describe hypothetical scenarios, not the design of this single-group study and not evidence of observed power. Distinguishing the purpose of a planning illustration from the purpose of a clinical result is essential for sound statistical interpretation.

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 important limitation for interpretation is that the registry record does not report an explicit result for the primary safety endpoint. Although it describes the endpoint and gives group-level adverse-event summaries, those summaries are not explicitly linked to the endpoint's event list and 7-day assessment window. The record therefore does not support a definitive endpoint-specific count or estimate.

The study has no comparator group and is not described as randomized. Its adverse-event summaries are descriptive and cannot establish a difference from another treatment or procedure. Study-wave labels do not create a valid control comparison. The registry record does not report an adjusted or comparative analysis.

Some design and analysis details are incomplete. The description of the Wave II roll-in analysis set is truncated, and the analysis population used for each outcome is not fully reported. Missing-data methods, follow-up completeness, endpoint adjudication, and sensitivity analyses are not reported in the registry record. These omissions make it difficult to assess how incomplete observation or classification decisions may affect the results.

The record lists several outcomes but gives no analysis results or multiplicity strategy. It does not provide endpoint estimates with confidence intervals. The serious-event term percentages are reported without corresponding event counts or a stated denominator in the summary, and it is not reported whether participants could appear under multiple terms. The planning assumptions are hypothetical and do not replace a documented sample-size justification for the trial. These limitations constrain both precision assessment and the scope of conclusions that can be drawn.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study for Treatment of Paroxysmal Atrial Fibrillation (PAF) by Pulsed Field Ablation (PFA) System With Irreversible Electroporation (IRE) — NCT04524364.
• Registry record last updated 2025-05-25; status last verified 2025-05.
• Results first posted 2024-05-14.
• 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

NCT04524364 is a completed, single-group device study of pulsed field ablation using irreversible electroporation for participants with paroxysmal atrial fibrillation. The registry lists an enrollment of 272, a start date of 2020-08-23, and primary completion on 2023-05-09. The stated primary endpoint is the number of participants with specified primary adverse events within 7 days after the procedure.

The record identifies Wave I, Wave II main phase, and Wave II roll-in groups and reports group-level serious adverse events, other adverse events, and deaths. It also lists secondary outcomes for acute procedural success, symptomatic atrial arrhythmia freedom from Day 91 to Day 365, and AFEQT score change. However, the registry record does not report an explicit primary-endpoint result, analyses, or a statistical analysis plan. With no comparator group, the design supports descriptive interpretation rather than a randomized treatment comparison.