Boston Scientific's Cryoballoon in the Treatment of Symptomatic Drug Refractory Paroxysmal Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Boston Scientific's Cryoballoon in the Treatment of Symptomatic Drug Refractory Paroxysmal Atrial Fibrillation (NCT04133168), a na na study. The primary outcome is Percentage of Participants With Freedom From Primary Safety Events at 12 Months Post-procedure (Acute and Chronic Events) Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter Models.

2. Clinical Question

This question concerns the observed safety event-free rate in a device-treated population, not a randomized estimate of benefit relative to another procedure or to no procedure. The study’s brief summary states that it was intended to establish safety and effectiveness for the device in the stated clinical setting. However, the registry record does not report the primary endpoint’s observed percentage or its confidence interval. Consequently, the record does not show how frequently participants met the event-free definition or how precisely that rate was estimated.

The registry describes ten outcome measures, including acute procedural success, freedom from reportable adverse events, freedom from safety events, and freedom from treatment failure. These are distinct outcomes and should not be treated as interchangeable with the primary safety endpoint. The posted primary question is specifically about freedom from a defined composite of safety events at twelve months. The record does not report a numerical primary result that would answer that question.

3. Trial Design

NCT04133168 is a completed Boston Scientific Corporation device study. The registry lists the phase as NA, allocation as NA, masking as none, and the model as single-group. Enrollment is listed as 458. The study started on 2020-06-24, and primary completion is listed as 2022-11-10. The stated purpose was to establish safety and effectiveness of the Boston Scientific Cardiac Cryoablation System for symptomatic, drug-refractory, recurrent, paroxysmal atrial fibrillation.

The intervention was a cardiac ablation procedure using the Boston Scientific Cardiac Cryoablation System. The registry identifies a Cryoablation arm and also lists FROzEN Non Roll In Treatment and Attempt Subjects, FROzEN Roll In Treatment Subjects, and POLARx FIT Treatment Subjects in its adverse-event material. These are not described as randomized comparison arms. The registry explicitly notes that the study is not a randomized comparison and that its arms are not a like-for-like control comparison. Differences between these groups therefore cannot, from the posted design information alone, be interpreted as causal treatment contrasts.

The primary outcome is a percentage of participants free from primary safety events at twelve months post-procedure. Its stated population is Non Roll-In Treatment and intent Subjects, and its event definition combines procedure-related and device-related events. The registry also lists secondary outcomes covering acute procedural success and freedom from adverse events, safety events, and treatment failure. The record names ten outcome measures overall but reports no analysis entries.

The single-group structure is important when interpreting the study’s purpose and evidence. It can describe outcomes observed among participants receiving the procedure, but it does not provide a randomized estimate of how those outcomes compare with an alternative. The record does not report the protocol’s sample-size justification, a detailed statistical analysis plan, interim analyses, or the participant flow for the primary endpoint. Those details should not be inferred from the enrollment number or from the listed adverse-event denominators.

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.

FROzEN AF Clinical Study

POLARx FIT Substudy

Analysis population for the primary outcome, as defined in the registry: Non Roll-In Treatment and intent Subjects

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 Percentage of Participants With Freedom From Primary Safety Events at 12 Months Post-procedure (Acute and Chronic Events) Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter Models, measured over 12 Months.

The primary endpoint is the percentage of participants free from primary safety events at twelve months after the procedure. The registry describes it as an observed safety event-free rate for Non Roll-In Treatment and intent Subjects. The composite includes procedure-related and device-related adverse events, with different event categories assigned different follow-up windows. The listed windows are seven days, thirty days, and twelve months. The specified categories include events such as death, myocardial infarction, stroke or cerebrovascular accident, vascular access complications, cardiac tamponade or perforation, atrial esophageal fistula, severe pulmonary vein stenosis, and persistent phrenic nerve palsy.

As a binary endpoint, each participant is classified according to whether the defined safety event criterion is met, and the group result is expressed as a percentage. A composite endpoint can capture several clinically important types of harm in one measure and can make the overall safety summary easier to interpret. Its meaning nevertheless depends on the components and their timing rules: the composite does not mean that all events are equally severe, equally frequent, or equally likely to occur.

The registry specifies a 95% confidence interval for this percentage, but the observed percentage and interval are not reported in the registry record. Without those values, the record does not give the estimated event-free rate or its statistical precision. The endpoint definition identifies what was intended to be measured, but it cannot by itself establish the observed safety experience.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what the registry’s endpoint and design would ordinarily mean. The explanations below are general; details of the methods actually used beyond what the registry states are not reported in the registry record.

What does a percentage endpoint represent?

A binary outcome places each participant into a defined category, such as meeting or not meeting an endpoint definition. A percentage summarizes the share of a specified population in that category. Here, the primary endpoint is the percentage free from primary safety events at twelve months. The registry states that the estimate is reported with a 95% confidence interval, but does not report either the percentage or the interval limits. The endpoint definition and the numerical estimate are separate pieces of information: knowing the former does not reveal the latter.

In general, a confidence interval describes uncertainty around an estimate under a particular statistical method and its assumptions. It is not a guarantee that the true value lies within the reported limits, nor does it measure clinical importance. The width of an interval is relevant to precision; the estimate and its interval need to be considered together. The registry record does not identify the interval-construction method, so a particular calculation method should not be assumed.

How should a composite endpoint be understood?

A composite combines multiple outcome types into a shared endpoint definition. This can provide a compact summary of whether participants remained free of any qualifying event. In this trial, the primary composite is described as procedure-related and device-related safety events, with listed components assigned event windows of seven days, thirty days, or twelve months. The specific component definitions matter because a participant may qualify as having an event through different pathways. A composite percentage alone would not describe the contribution, frequency, or severity of each component.

For that reason, a composite result is best understood alongside component-specific reporting and clear definitions of how events were assessed. The registry gives a detailed description of event categories and time windows, but it does not report component-specific primary endpoint results. It also does not report the adjudication process or additional operational details for deciding whether a reported event met each criterion. Those methods are not reported in the registry record.

What does a single-group design estimate?

A single-group study can describe the observed outcomes among participants who received the intervention. It does not create a randomized contrast between treatment strategies. Randomization is generally used to balance measured and unmeasured characteristics between groups, supporting a causal comparison when the trial is appropriately conducted and analyzed. Here, allocation is listed as NA, the model is single-group, and the registry states that the arms are not a like-for-like control comparison. A difference between the listed groups, if calculated elsewhere, would not automatically be an unbiased treatment effect.

Masking is listed as none. In general, masking can reduce the influence of knowledge of treatment assignment on some aspects of care, outcome assessment, or reporting. Its relevance varies by outcome and study procedures. The record does not provide additional details about outcome assessment or independent event adjudication, so those processes should not be inferred from the masking entry.

Why do event counts and participant counts differ in meaning?

A count of participants affected answers how many people had at least one event of a defined kind, while an event count may include repeated events in the same person. The adverse-event information identifies numbers at risk and numbers affected for serious and other events. It does not specify in the registry record whether all event listings count unique participants, repeated events, or both, so those details should not be presumed. The primary endpoint is framed as a percentage of participants, which is conceptually distinct from a total count of event episodes.

Follow-up also matters for interpreting a fixed-time percentage. A twelve-month endpoint requires a rule for participants whose status at that time is unavailable. General approaches to missing endpoint data can lead to different estimates, depending on the reasons data are missing and the assumptions made. The registry record does not report missing-data handling, follow-up completeness, or the number of participants included in the primary endpoint analysis. It is therefore not possible to assess how those factors affected the endpoint estimate.

What analysis details are available?

The record specifies a 95% confidence interval for the primary percentage and lists ten outcome measures. It lists zero analyses. The specific statistical model, interval method, analysis population rules, covariate adjustment, hypothesis-testing procedure, and multiplicity strategy are not reported in the registry record. No particular method should be attributed to the trial without that information.

General statistical planning can also be distinguished from trial results. The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. This is a planning illustration, not a report of the trial’s design justification, not an observed power calculation, and not evidence that the study had a comparator. The record does not report the trial’s own sample-size justification. No sample-size conclusion about adequacy can be drawn from the planning assumptions alone.

Overall, statistical interpretation depends on both a clearly specified endpoint and accessible numerical results with analysis details. The endpoint definition is present, but its estimate and interval are not. The single-group design supports descriptive interpretation of outcomes in the treated population, while the missing analysis and follow-up details constrain assessment of precision and completeness.

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("FROzEN Non Roll-In Subjects")
n      <- c(326)
events <- c(313)
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  FROzEN Non Roll-In Subjects  326  313  96.0  93.3  97.9  93.3  97.7  93.3  97.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ten outcome measures, including the primary safety endpoint and secondary outcomes related to acute procedural success, freedom from reportable adverse events, freedom from safety events, and freedom from treatment failure. Considering multiple outcomes raises a general statistical issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which outcomes were intended to support confirmatory claims. No claim about adjustment, or lack of adjustment in the actual analysis, should be inferred beyond that absence of reporting.

The record lists zero analyses and does not provide a numerical primary endpoint result. It therefore does not report the statistical test, if any, used for the primary outcome, or whether any secondary outcomes were formally tested. No interim analyses are reported in the registry record. The protocol’s statistical analysis plan is not reported in the registry record.

Missing data are also important for a twelve-month endpoint. In general, participants without known endpoint status may affect an estimated percentage, and different handling assumptions can produce different results. The record does not report follow-up completeness, the number with an available twelve-month assessment, missing-data rules, or sensitivity analyses. Those details are not reported in the registry record, so the potential impact of missing outcome information cannot be assessed.

The primary endpoint population is described as Non Roll-In Treatment and intent Subjects, while the adverse-event listings include separate non-roll-in, roll-in, and POLARx FIT groups. The registry does not report a complete participant flow or explain in detail how the endpoint analysis population relates to every listed group. Nor does it state the analysis-set rules for each outcome. These population details are necessary for judging who contributed to each estimate, but they 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal (3.3%), cancer (3.3%), hematological (3.3%), atrial fibrillation (2.0%), coronary artery disease (2.0%).

The adverse-event listing separates participants by named group and reports numbers at risk, numbers affected by serious adverse events, numbers affected by other adverse events, and deaths. For FROzEN Non Roll In Treatment and Attempt Subjects, 326 were at risk for each event category; 33 were affected by serious adverse events, 86 by other adverse events, and 1 death is listed. For FROzEN Roll In Treatment Subjects, the corresponding figures are 60 at risk, 10 affected by serious adverse events, 16 affected by other adverse events, and 1 death. For POLARx FIT Treatment Subjects, the figures are 50 at risk, 4 affected by serious adverse events, 5 affected by other adverse events, and 0 deaths.

These are descriptive counts, not randomized comparisons. The registry warns that the arms are not a like-for-like control comparison, so the figures should not be treated as evidence that one group had a higher or lower risk because of its device or procedure. The record does not explain whether affected participants could appear in more than one event category, and the serious and other event counts should not be added or otherwise combined.

The most frequent serious-event terms listed are Gastrointestinal, Cancer, and Hematological at 3.3% each; Atrial Fibrillation, Coronary Artery Disease, and Sinus Bradycardia are each listed at 2.0%. These terms describe categories in the adverse-event listing; they are not the primary endpoint result. The primary endpoint’s event-free percentage and confidence interval are not reported in the registry record.

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

The registry record documents a completed, single-group device study designed to assess safety and effectiveness of the Boston Scientific Cardiac Cryoablation System in symptomatic, drug-refractory, recurrent, paroxysmal atrial fibrillation. It defines a primary safety endpoint as freedom from a composite of procedure-related and device-related events at twelve months. It also gives group-level adverse-event counts and selected serious-event terms. These details describe the study question and some posted safety information.

The record does not report the primary endpoint’s observed event-free percentage or 95% confidence interval. It therefore does not establish, from the posted primary outcome data, the frequency of participants meeting that definition or the precision of an estimate. The description of an endpoint is not itself a result. The group-level adverse-event counts provide separate descriptive information and should not be substituted for the primary outcome.

The single-group design also limits what the study can establish comparatively. Without a randomized comparator, the record does not provide a controlled estimate of how outcomes differ from another procedure or from no procedure. The registry explicitly states that the listed groups are not a like-for-like control comparison. Differences across those groups cannot be interpreted as causal treatment effects on the basis of the design information reported.

The word effectiveness appears in the study’s stated purpose, but the record does not provide a numerical primary effectiveness result in the registry record described. Secondary outcomes include acute procedural success and freedom from treatment failure, yet their numerical results are not reported in the registry record. The presence of those outcome definitions does not establish their observed values.

In general, a study result is most informative when its population, endpoint, estimate, uncertainty, missing-data handling, and analysis methods are all clear. Several of those elements are either not reported or unavailable in the registry record. The appropriate reading is therefore limited: the record describes the design, endpoint definitions, and adverse-event listings, but does not support a numerical conclusion about the primary safety endpoint or a comparative claim about treatment effects.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and numerical results must be read separately. The registry describes a twelve-month event-free safety endpoint and specifies a 95% confidence interval, but does not report the estimate or its interval limits. A precise endpoint definition helps clarify what a result would mean; without the result, readers cannot judge the observed rate or its precision.

The design also matters statistically. A single-group study can characterize outcomes among participants receiving a device procedure, but it does not supply the randomized comparison needed to isolate a treatment contrast. The registry’s explicit warning that the groups are not like-for-like reinforces the need to keep descriptive safety summaries distinct from comparative claims. This is especially important when several named groups and device categories appear in the adverse-event material.

The composite endpoint provides another useful statistical lesson. Combining procedure-related and device-related events into an event-free measure offers an overall summary, while its components can differ in type and timing. A composite percentage would not, on its own, explain which events occurred or how the component events contributed. Component-level reporting and clear analysis-population information are valuable for understanding what an aggregate estimate represents.

Finally, the record shows how missing analysis details affect interpretation. It lists multiple outcomes but does not report a multiplicity strategy, missing-data handling, or the primary analysis population’s numerical result. These omissions prevent readers from evaluating the full statistical evidence, even though enrollment, study status, endpoint definitions, and adverse-event counts are recorded. The study is statistically informative as an example of the distinction between a planned measurement and a reported estimate, and between descriptive evidence and causal comparison.

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 this particular registry record is that the primary endpoint’s result is not reported. The endpoint is defined and a 95% confidence interval is specified, but neither the observed percentage nor the interval limits are available. This prevents assessment of the event-free rate and its precision.

The single-group design and allocation listed as NA mean the study does not provide a randomized control comparison. The registry explicitly says that the arms are not a like-for-like control comparison. The listed adverse-event groups therefore cannot be treated as equivalent groups for estimating causal differences. Masking is listed as none; additional details about outcome assessment are not reported in the registry record.

The primary endpoint population is described as Non Roll-In Treatment and intent Subjects, whereas the adverse-event listing includes non-roll-in, roll-in, and POLARx FIT groups. The registry does not report a full participant flow or explain in detail how the endpoint population maps onto those listings. Enrollment is recorded as 458, but enrollment does not itself establish the number analyzed for the primary endpoint or the completeness of twelve-month follow-up.

The record does not report the statistical analysis plan, the trial’s sample-size justification, analysis-set rules, missing-data handling, sensitivity analyses, or multiplicity strategy. It also does not report component-specific primary endpoint results. These are reporting limitations of the registry record; their absence does not establish what procedures were or were not used outside the information recorded there. Together, they constrain assessment of the endpoint estimate, its precision, and the relationship between the primary outcome and the adverse-event summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Boston Scientific's Cryoballoon in the Treatment of Symptomatic Drug Refractory Paroxysmal Atrial Fibrillation — NCT04133168.
• Registry record last updated 2025-04-03; status last verified 2025-03.
• Results first posted 2023-12-07.
• 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

NCT04133168 is a completed, single-group device study sponsored by Boston Scientific Corporation. It lists enrollment of 458, start on 2020-06-24, and primary completion on 2022-11-10. The study’s stated aim was to assess safety and effectiveness of the Boston Scientific Cardiac Cryoablation System for symptomatic, drug-refractory, recurrent, paroxysmal atrial fibrillation.

The primary outcome is the percentage of Non Roll-In Treatment and intent Subjects free from primary safety events at twelve months. The registry specifies a 95% confidence interval but does not report the primary estimate or interval limits. Adverse-event counts are listed for FROzEN Non Roll In Treatment and Attempt Subjects, FROzEN Roll In Treatment Subjects, and POLARx FIT Treatment Subjects. The registry notes that these groups are not a like-for-like control comparison. Detailed statistical methods, missing-data handling, and the primary analysis population’s outcome are not reported in the registry record.