Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF (NCT04198701), a non-randomized na study. The primary outcome is Safety: Number of Participants With at Least One Primary Safety Event.

2. Clinical Question

The clinical question is about the frequency of predefined safety events in a treated population, rather than whether the device is better than another treatment. The endpoint is a participant count: someone with one or more qualifying events is counted as having the outcome. The registry record also lists changes in EQ-5D and AFEQT quality-of-life scores as secondary outcomes, but does not report their results. It does not report a comparison against an untreated or randomized control population.

3. Trial Design

This was a prospective, multi-center, non-randomized, unblinded worldwide pre-market clinical study of the PulseSelect PFA System. The registry describes a sequential study model with distinct Pilot and Pivotal phases, each forming a separate data set to be analyzed and reported according to the study objectives. Allocation was non-randomized and masking was none. The record lists the phase as NA.

The study enrolled 421 participants. It began on 2019-12-10, had a primary completion date of 2022-11-28, and is listed as completed. The sponsor was Medtronic Cardiac Ablation Solutions. The stated purpose was to gather safety and effectiveness data and first-in-human information about clinical safety and device function for pulmonary vein isolation in the treatment of atrial fibrillation.

The registry distinguishes four groups: Pilot; Pivotal - Roll-In; Pivotal - Paroxysmal AF; and Pivotal - Persistent AF. Pilot patients were the first group enrolled. Roll-in patients were the first treated by each physician in the pivotal phase. The paroxysmal and persistent groups consisted of non-roll-in patients, categorized by atrial fibrillation type. These categories describe enrollment and disease characteristics; the record does not describe them as randomized arms.

The primary safety endpoint applies specifically to non-roll-in pivotal patients who had a pulsed field ablation procedure, not automatically to every participant enrolled in the study. The record does not report the protocol’s detailed statistical analysis plan, allocation procedures beyond non-randomization, or the rationale for the planned enrollment. Those details 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

Analysis population for the primary outcome, as defined in the registry: Non roll-in pivotal patients that had a Pulsed Field Ablation procedure.

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 Safety: Number of Participants With at Least One Primary Safety Event, measured over up to 6 months.

The primary endpoint is the number of participants with at least one primary safety event, measured in participants and assessed up to 6 months. It applies to non-roll-in pivotal patients who had a pulsed field ablation procedure. The endpoint is a participant-level count: a participant meeting one or more listed event criteria contributes to the outcome.

The event definition includes pulmonary vein stenosis with at least 70% diameter reduction, phrenic nerve injury or diaphragmatic paralysis ongoing at 6 months, and atrioesophageal fistula within 6 months post-ablation. A separate group of events is assessed within 30 days of the procedure: cardiac tamponade or perforation, cerebrovascular accident, major bleeding requiring transfusion, myocardial infarction, pericarditis requiring intervention, transient ischemic attack, specified vagal nerve injury, vascular access complications requiring intervention, systemic or pulmonary embolism requiring intervention, pulmonary edema, death, and specified cardiovascular or pulmonary adverse events related to the system or procedure that prolong or require hospitalization for more than 48 hours, excluding recurrent AF, AFL, or AT.

As a general statistical concept, a composite safety endpoint can capture several types of clinically important events in one participant-level measure. That can make an overall safety summary easier to interpret, but the component events can differ in nature and seriousness. The registry record does not report the primary endpoint result or component-specific results, so the frequency of this defined outcome cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-randomized, unblinded, sequential study with separate Pilot and Pivotal phases. The primary outcome is binary at the participant level: each eligible participant either had at least one qualifying event or did not, according to the endpoint definition. The posted endpoint unit is participants, and the measure is a count of participants, not a rate per unit of follow-up time.

What does a participant-level safety endpoint capture?

As a general statistical explanation, a participant-level endpoint counts people who meet a defined outcome, regardless of whether they experience one qualifying event or more than one. This approach can summarize the proportion of a study population with any event, but it does not describe the number of events per person. A count of affected participants and a count of all individual event occurrences answer different questions. The endpoint definition also matters: an event must meet the listed type, timing, and, where specified, severity or intervention criteria to qualify.

The primary endpoint combines events within 6 months post-ablation with other events assessed within 30 days. Some events have additional conditions, such as phrenic nerve injury or diaphragmatic paralysis ongoing at 6 months, major bleeding requiring transfusion, or a procedure- or system-related cardiovascular or pulmonary event requiring or prolonging hospitalization for more than 48 hours. An endpoint with multiple components can provide an overall summary, but the overall count alone cannot show which component accounts for the outcome. Component-level results are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes the range of values compatible with the observed data under a specified statistical method. A narrow interval indicates greater precision than a wide one, but neither width nor statistical significance establishes causality. The registry record does not report a primary endpoint estimate or confidence interval. There is therefore no posted interval from which to assess the precision of the primary safety result.

For a binary outcome, the observed count depends on both the number of participants with an event and the number assessed. Interpretation also depends on how missing outcome information and follow-up were handled. The record identifies the target population and endpoint window, but does not report the analysis population counts, missing-data methods, or participant-level completion of follow-up. These omissions prevent a full assessment of the denominator used for the primary analysis.

What do the planning illustrations represent?

General sample-size calculations translate an assumed effect and analysis method into a planning target; they do not describe outcomes actually observed. The planning assumptions associated with the posted illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are based on fractions of an observed effect. For non-time-to-event outcomes, the stated convention is participants per arm; time-to-event illustrations instead use a total number of events.

Those conventions are planning assumptions, not evidence that the study used a randomized two-arm design. The trial itself is described as non-randomized, with groups defined by study phase, roll-in status, or AF type. A planning calculation based on an effect from observed data does not show that a particular sample size was prospectively justified, nor does it establish the probability that the study would detect an effect. Sample-size illustrations are not observed power. The registry record does not report the study’s own sample-size justification or the analysis plan behind these calculations.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular relationship between the mean and variability. Over-dispersion means the observed variability is greater than that assumed by a simpler model. If it is ignored, estimated uncertainty can be too small and tests can appear more conclusive than warranted. This general issue is most relevant when modeling event counts or rates; it is distinct from the primary participant-level binary endpoint. The registry record does not report a model or an over-dispersion assessment for the primary endpoint.

In general, the choice of analysis should follow the endpoint, study design, and data structure. A non-randomized comparison requires care because group differences can reflect factors other than treatment. For the posted record, the analysis methods and primary endpoint results are not reported in the registry record, and the number of reported analyses is listed as zero. Thus, no inferential result for the primary endpoint can be evaluated from the 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("Pivotal - Paroxysmal AF", "Pivotal - Persistent AF")
n      <- c(150, 150)
events <- c(1, 1)
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  Pivotal - Paroxysmal AF  150  1  0.7  0.0  3.7  0.1  3.7  0.2  3.6
ARM  Pivotal - Persistent AF  150  1  0.7  0.0  3.7  0.1  3.7  0.2  3.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and identifies two secondary quality-of-life outcomes: change in EQ-5D score and change in AFEQT score. It does not report results for those outcomes. The record also lists zero analyses, so it does not provide statistical tests, confidence intervals, or model outputs for evaluating the primary or secondary outcomes.

When a study assesses multiple outcomes or multiple components, the chance of at least one apparently unusual result can increase if each is tested separately. As a general statistical principle, multiplicity procedures or a prespecified hierarchy can help control how results are interpreted across several tests. Whether such procedures were planned or used is not reported in the registry record. The registry description of multiple outcomes alone does not establish how multiplicity was handled.

Missing data are also important for participant-level safety outcomes, especially when follow-up extends up to 6 months. The record does not report how many participants completed the relevant follow-up, whether any primary endpoint observations were missing, or how missing outcome information was treated. It does not report whether participants were included according to a particular analysis population definition or how deviations from the planned procedure were handled.

The primary endpoint specifies non-roll-in pivotal patients who had a pulsed field ablation procedure, but the registry does not give the primary analysis denominator or the number assessed for each event window. Without those details, the completeness of outcome ascertainment and the handling of incomplete follow-up cannot be judged. The protocol’s statistical plan, multiplicity strategy, and missing-data approach are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (21.1%), atrial flutter (8.3%), bradycardia (2.6%), cardiac arrest (2.6%), dysphagia (2.6%).

The adverse-event summaries divide participants into Pilot, Pivotal - Roll-In, Pivotal - Paroxysmal AF, and Pivotal - Persistent AF groups. For each group, the record lists participants at risk and participants affected by serious adverse events, as well as participants at risk and affected by other adverse events. It separately lists one death in each group. These are descriptive counts and should be read within the group labels and denominators given.

The most frequently listed serious adverse-event terms are atrial fibrillation at 21.1% and atrial flutter at 8.3%. Bradycardia, cardiac arrest, dysphagia, and cellulitis are each listed at 2.6%. The registry record does not provide enough detail in these entries to determine whether participants experienced more than one term, how terms were defined or attributed, or whether the term percentages use the same denominator as the group summaries.

These adverse-event figures should not be equated with the primary safety endpoint. The primary endpoint has specified event criteria and time windows, whereas the adverse-event summaries are not described as a direct accounting of those criteria. A death count also does not establish cause or relationship to treatment. The posted figures are safety descriptions, not proof that the device or procedure caused any event.

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

The record describes a clinical study of a pulsed field ablation device in people with atrial fibrillation, with safety and effectiveness as its stated aims. It identifies a participant-level primary safety endpoint and defines qualifying events across two follow-up windows. It also reports adverse-event counts for Pilot and Pivotal groups and lists serious adverse-event terms.

What the record does not provide is the primary endpoint result, an estimate of its uncertainty, or a statistical comparison with a control group. The listed adverse-event counts cannot fill that gap because the registry does not establish that they represent the primary endpoint definition or its target population. Nor can the group counts establish that outcomes differ because of treatment: the study was non-randomized, and group membership reflects study phase, physician roll-in status, or AF type.

The reported deaths and adverse-event terms should be interpreted descriptively. The record does not state whether events were judged related to the device or procedure, provide event-level timing and detail, or clarify participant overlap across terms. The counts therefore cannot establish causation, and they should not be treated as a complete accounting of every clinical outcome.

The registry also lists changes in EQ-5D and AFEQT scores as secondary outcomes but does not report those results. Without primary and secondary outcome estimates, uncertainty intervals, and analysis details, the posted record cannot support a conclusion about the size or precision of any treatment effect. The completed status and enrollment total describe study conduct, not the magnitude or certainty of an outcome.

In general, non-randomized studies can describe outcomes in a treated population, but comparisons between non-randomized groups may reflect differences in who entered each group or when they were enrolled. That concern applies to the study’s Pilot and Pivotal categories and to the paroxysmal and persistent AF groups. The available registry information supports a cautious account of design and reported adverse-event counts, not a causal or comparative conclusion.

14. Why This Trial Matters Statistically

This study is statistically notable for its combination of a clinically defined, participant-level safety endpoint with a sequential, non-randomized design. The distinction between the broad enrolled population and the narrower primary endpoint population is important: the primary safety question applies to non-roll-in pivotal patients who underwent the procedure, while adverse-event summaries are presented across all four listed groups.

The study also illustrates why endpoint definitions and event windows matter. Some qualifying outcomes are assessed within 30 days, while others are assessed within 6 months or require persistence at 6 months. A single overall participant count could provide a compact safety summary, but component-level information is needed to understand which events contribute. The registry defines the composite outcome but does not report its result or component counts.

Its non-randomized allocation also limits the interpretation of differences among groups. Pilot, roll-in, paroxysmal AF, and persistent AF categories serve different roles in the study structure; they are not interchangeable randomized arms. Statistical adjustment could address measured differences in some settings, but the record does not report an adjusted comparison or the analysis methods needed to assess one.

Finally, the registry lists secondary quality-of-life measures and separate adverse-event summaries, yet does not report outcome analyses for the primary or secondary measures. This makes transparency about missing results and uncertainty especially important. The record provides design and safety-reporting context, but the absence of primary endpoint estimates means that the central safety question remains unquantified in the posted registry information.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting the study results is that the registry record does not report the primary safety endpoint result. It also does not report a confidence interval, component-specific primary event counts, or the primary analysis denominator. Although adverse-event counts are listed, the record does not establish that they match the endpoint’s eligibility criteria, event definitions, or follow-up windows.

The study was non-randomized and unblinded, and the groups reflect phase, physician roll-in status, or AF type. They therefore do not constitute a like-for-like randomized comparison. Any differences across groups could relate to those features or other differences in participants and study conduct. The registry does not report an adjusted comparison that would help evaluate such differences.

The registry record does not report details needed to assess outcome ascertainment and analysis, including the statistical analysis plan, missing-data handling, the number completing follow-up, analysis population definitions, or multiplicity procedures. It does not report the rationale for the planned enrollment. The listed death counts and adverse-event terms do not provide attribution or enough event-level information to determine causality or overlap.

The study is described as worldwide, multi-center, prospective, and pre-market, but the record does not provide site-level information or details of participant characteristics beyond the AF group descriptions. Generalizability across patient populations and clinical settings cannot be assessed from these details alone. The listed planning assumptions do not remedy these limitations: sample-size illustrations are planning calculations, not a substitute for reported outcome estimates or evidence of prospective design justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF — NCT04198701.
• Registry record last updated 2025-02-13; status last verified 2025-02.
• Results first posted 2023-12-13.
• 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 describes a prospective, multi-center, non-randomized, unblinded worldwide pre-market study of the Medtronic PulseSelect Pulsed Field Ablation System for atrial fibrillation. It enrolled 421 participants, began on 2019-12-10, reached primary completion on 2022-11-28, and is listed as completed. The study used Pilot and Pivotal phases with four groups defined by study phase, roll-in status, or AF type.

The primary safety endpoint is the number of non-roll-in pivotal patients with at least one predefined safety event, assessed up to 6 months. The registry defines events and follow-up windows but does not report the primary endpoint result, its precision, or a statistical analysis. Adverse-event counts and serious-event terms are listed by group, but they should not be treated as the primary endpoint or as randomized comparisons. Results for the listed quality-of-life outcomes are not reported in the registry record.