AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation (NCT00560885), a na phase 3 study. The primary outcome is Percent of Patients Free From AF and Off Class I and III Anti-arrhythmic Drugs as Determined by Holter Monitoring at 6 Months..

2. Clinical Question

3. Trial Design

The registry record identifies NCT00560885 as a Phase 3, prospective, non-randomized, multi-center clinical trial of the AtriCure Bipolar System for treating permanent atrial fibrillation during concomitant on-pump cardiac surgery. The listed enrollment is 55. The record lists the trial status as completed, with a start date of 2007-11 and primary completion date of 2009-12.

The design is single-group, and allocation is listed as not applicable. Masking is listed as none. These features mean the study does not provide a randomized, masked comparison between the device and a control intervention. Its main efficacy question is therefore about the outcome observed in the treated study group, not an estimated treatment difference against a concurrent comparator.

The intervention is the AtriCure Bipolar System. The arm description says that the Synergy Bipolar Ablation system was used to create lesions outlined in the Maze IV procedure during concomitant open cardiac surgery. The registry summary frames the purpose as demonstrating safety and effectiveness in this surgical setting. That stated purpose does not itself establish whether the endpoint was achieved.

The record lists four outcome measures, including the primary endpoint and secondary outcomes concerning freedom from atrial fibrillation independent of anti-arrhythmic drug status at 6 months, and a composite 6-month post-procedure major adverse event rate. The primary endpoint is specifically freedom from atrial fibrillation while off Class I and III anti-arrhythmic drugs, assessed by Holter monitoring at 6 months post procedure.

The registry record does not report the primary endpoint result, its confidence interval, or analysis-level efficacy estimates. It also does not report a statistical analysis plan, sample-size justification, or interim analyses. Those omissions prevent a full assessment of how the observed endpoint was analyzed or how the study's planned precision was determined.

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: Subjects were screened for enrollment and consented prior to being brought to the OR with the potential that they may not be eligible based on some criteria evaluated in OR (i.e. left atrial size assessed by TEE). 1 subject was found to have LA size that excluded them from the trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population included subjects that were evaluable for the Primary Efficacy Endpoint. The completer population excluded 5 subjects. These were 2 post op deaths, 2 deaths beyond 3 months but less than 6 months and 1 subject that withdrew at the 30 day visit.

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 Percent of Patients Free From AF and Off Class I and III Anti-arrhythmic Drugs as Determined by Holter Monitoring at 6 Months., measured over 6 Months Post Procedure.

The primary endpoint is the percentage of patients who were free from atrial fibrillation and off Class I and III anti-arrhythmic drugs at 6 months post procedure, with rhythm status determined by Holter monitoring. It combines a clinical rhythm criterion with a medication criterion. A patient must satisfy both parts for the endpoint definition to be met; freedom from atrial fibrillation alone is not enough.

This kind of endpoint can be useful when the research question concerns both documented rhythm status and reliance on specified anti-arrhythmic drug classes. Holter monitoring provides a defined method of assessing rhythm over the monitoring period, while the medication condition makes the endpoint more stringent than a rhythm-only measure. These are general features of endpoint interpretation, not evidence that the endpoint was reached in this trial.

The record specifies a 95% confidence interval as the measure of dispersion for the primary endpoint, but does not report the observed percentage or the interval limits. A confidence interval generally conveys the precision of an estimated outcome under the analysis assumptions; it is not a guarantee about an individual patient's outcome. Without the estimate and interval, neither the observed endpoint level nor its precision can be assessed from the registry record.

The analysis population included subjects evaluable for the primary efficacy endpoint. The registry record does not give the number included in that population, the operational rules for being evaluable, or the endpoint value. These details matter because an endpoint percentage depends on how the population and missing endpoint assessments are handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, the central descriptive quantity is typically the outcome observed among participants receiving the intervention. It is not, by itself, a contrast between two treatment strategies. A randomized comparison can help estimate how outcomes differ between assigned groups, because random allocation is intended to make groups comparable on average. This trial is described as non-randomized, with allocation listed as not applicable and no control group identified. Its registry record therefore supports a description of the treated group, not a direct randomized treatment-effect estimate.

This distinction matters even when an outcome is measured carefully. Holter monitoring defines how atrial fibrillation status was assessed for the primary endpoint, but a measurement method does not create a comparison group. Nor does the trial's stated aim of demonstrating safety and effectiveness supply a numerical criterion or establish that the aim was met. The record does not report a prespecified success threshold or an inferential comparison against such a threshold.

How should the endpoint percentage be understood?

The primary outcome is a percentage of subjects meeting a specific condition at 6 months post procedure. In general, a percentage of this kind is determined by identifying the analysis population, classifying each subject according to the endpoint definition, and relating the number meeting the definition to the population assessed. Here, the endpoint requires both freedom from atrial fibrillation and being off Class I and III anti-arrhythmic drugs. The record does not report the number meeting that definition, the denominator used for the primary analysis, or the resulting percentage.

A percentage should always be read together with its population definition and the treatment of subjects whose status is unavailable. If subjects with missing assessments are excluded, the estimate describes those assessed; if a prespecified rule classifies missing status differently, the estimate may have a different meaning. The registry record says the primary efficacy analysis population included evaluable subjects, but it does not give the criteria for evaluability or explain the handling of missing Holter data. No specific missing-data method can therefore be attributed to this analysis.

What information does a confidence interval add?

The record identifies a 95% confidence interval as the dispersion measure for the primary endpoint. In general, a confidence interval expresses sampling uncertainty around an estimated quantity under a particular statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval for the same type of estimate, although precision does not determine whether an outcome is clinically important. The interval also does not describe the range of outcomes expected for every individual patient.

The confidence-interval level alone does not reveal the endpoint estimate, the interval's width, or whether an analysis crossed a decision threshold. Since neither the percentage nor the interval limits are reported, readers cannot assess those properties for this trial. The record likewise does not state the interval calculation method, such as whether it used a particular approximation or adjustment. That method is not reported in the registry record.

Why do analysis populations matter?

Analysis-population definitions determine which subjects contribute to an estimate and therefore shape the question that estimate answers. An evaluable population generally consists of subjects with information considered adequate for the relevant endpoint, but the exact meaning depends on the protocol and analysis rules. A completer population instead typically refers to subjects who completed specified follow-up, though the registry record's own description should govern interpretation in this study. It says that the completer population excluded five subjects, with the reasons and timing stated in the endpoint description.

The record does not say whether the primary endpoint analysis used the completer population, a separate evaluable population, or another defined set beyond noting that the primary analysis included evaluable subjects. It also does not report an intention-to-treat analysis or describe how deaths and withdrawal were incorporated into each outcome. These distinctions are especially relevant when a status is measured at a follow-up time and some subjects do not contribute an assessment at that time.

What can be inferred from the absence of analysis results?

The registry record lists zero analyses and supplies no primary efficacy estimate or confidence interval. This means there are no posted analysis results from which to evaluate the observed efficacy endpoint. It does not demonstrate that an analysis was never performed; it means that an analysis result is not reported in the registry record. The statistical analysis plan, interim analyses, and sample-size justification are also not reported in the registry record.

The record contains assumptions for a planning illustration based on an observed effect, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect, and says participant counts are per arm except for time-to-event outcomes. These are planning assumptions, not evidence that this single-group trial was designed with those assumptions, and the record provides no resulting sample-size values. The planning illustration cannot be read as observed power or as a description of the trial's own design.

More generally, a planning calculation describes a hypothetical future study under specified assumptions. It does not establish the probability that the completed study found a true effect, nor does it replace an effect estimate and uncertainty interval. Since the primary result is absent, no recalculation from posted summary statistics is available. The registry record does not report a discrepancy between a sponsor analysis and a recalculation.

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("AtriCure Bipolar System")
n      <- c(50)
events <- c(37)
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  AtriCure Bipolar System  50  37  74.0  59.7  85.4  60.4  84.1  60.4  84.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including the primary efficacy endpoint and secondary outcomes concerning freedom from atrial fibrillation independent of anti-arrhythmic drug status and a composite 6-month post-procedure major adverse event rate. Considering several outcomes can raise a multiplicity question: when multiple statistical tests are conducted, the chance of at least one apparently unusual result can differ from the chance associated with a single test. This is a general statistical issue, not a finding about this study.

The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan. It is therefore not possible to determine whether the outcome analyses were adjusted, ordered, or treated as descriptive. The primary endpoint is identified, but that designation alone does not establish a particular testing procedure.

Missing-data interpretation also depends on the analysis population and the rules for unavailable endpoint measurements. The primary efficacy population is described as subjects evaluable for the endpoint. The completer population excluded five subjects: two post-operative deaths, two deaths beyond 3 months but less than 6 months, and one subject who withdrew at the 30-day visit. The record does not state how these subjects were treated in the primary endpoint analysis, whether additional assessments were missing, or what method was used to address missing data.

Because the endpoint is assessed at 6 months, subjects without an evaluable status at that time may affect the estimate depending on the analysis rules. The registry record does not report sensitivity analyses or alternative assumptions about missing outcomes. It also does not give the denominator for the primary estimate. These omissions limit assessment of the robustness and population scope of any efficacy result, which is itself not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: haemorrhage (21.8%), cardiac failure congestive (20.0%), pleural effusion (18.2%), respiratory failure (16.4%), bradycardia (14.5%).

The registry record lists 55 subjects at risk for serious adverse events in the AtriCure Bipolar System group and 45 affected by serious adverse events. For other adverse events, it lists 55 at risk and 51 affected. These are the registry's group-level counts; they should be read as separate safety summaries, not added together. The record does not report deaths in the adverse-event summary.

The listed serious-event terms and percentages are haemorrhage, 21.8%; cardiac failure congestive, 20.0%; pleural effusion, 18.2%; respiratory failure, 16.4%; bradycardia, 14.5%; and renal failure, 12.7%. These values are presented as event-term frequencies in the registry record. The record does not specify in this summary whether a subject could contribute to more than one term, nor does it provide additional detail about event severity, timing, relatedness to the device or procedure, or duration.

Adverse events observed during concomitant cardiac surgery and follow-up cannot be attributed to the device on the basis of these counts alone. The study has no randomized control group for comparison, and the registry record does not report comparative safety estimates. These counts describe the recorded safety experience; they do not establish a causal relationship or quantify excess risk versus another treatment.

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

The registry record defines an important, specific endpoint: freedom from atrial fibrillation while off Class I and III anti-arrhythmic drugs at 6 months post procedure, assessed by Holter monitoring. It also describes a prospective, non-randomized, multi-center, single-group study in the setting of concomitant on-pump cardiac surgery. Those details clarify what was studied and what outcome the primary question was meant to address.

What the record does not communicate is the observed primary endpoint percentage or its 95% confidence interval. As a result, it cannot establish from the posted results how often the endpoint was met or how precisely that percentage was estimated. The absence of a reported result is not a positive or negative efficacy finding; it is an information gap in the registry record. The stated purpose of demonstrating safety and effectiveness should not be mistaken for a reported demonstration.

The design also determines the scope of interpretation. Because the trial is single-group and non-randomized, it cannot offer a direct randomized comparison against another treatment. An outcome observed after the procedure could reflect the intervention, the concomitant surgery, other care, participant characteristics, or multiple influences together. The record does not supply a comparative framework that would distinguish those possibilities.

The efficacy question also has a narrower meaning than a rhythm-only endpoint. A patient must be free from atrial fibrillation and off the specified drug classes to meet the primary definition. The separate secondary outcome concerning freedom from atrial fibrillation independent of drug status asks a different question. Neither result is reported in the registry record.

The safety counts document adverse events in the study group, including serious adverse events and the listed terms. Without a comparison group, those observations cannot determine whether the device increased or reduced event risk. Overall, the registry entry supports a description of the trial's design, endpoint definitions, exclusions, and recorded safety counts; it does not support a numerical efficacy conclusion or a causal comparative claim.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and endpoint definition shape the claims a study can support. The primary endpoint is not simply a rhythm measure: it requires both freedom from atrial fibrillation and being off specified anti-arrhythmic drug classes at 6 months. That distinction makes the endpoint definition central to interpretation and prevents it from being conflated with the separate secondary question about rhythm status regardless of drug use.

The study's single-group, non-randomized design also illustrates the difference between describing an outcome and estimating a comparative treatment effect. A treated-group result, if reported, could characterize the observed experience in that group. Without a randomized comparator, it would not directly quantify how the result differs from what would have occurred under another treatment strategy. Statistical precision cannot remove this design limitation.

The record further illustrates why an endpoint result needs its analysis population, denominator, and uncertainty measure. It identifies evaluable subjects as the primary efficacy population and specifies a 95% confidence interval, but does not report the endpoint estimate, interval limits, or analysis denominator. Without those elements, readers cannot assess either the magnitude or precision of the primary outcome.

The distinction between the evaluable and completer populations is also relevant. The record describes five exclusions from the completer population, including deaths and a withdrawal. How such cases enter an endpoint analysis can affect what population an estimate represents. The registry entry does not provide enough detail to resolve that question.

Finally, the safety data and efficacy question answer different descriptive needs. Safety counts identify recorded events in the study group, while the primary endpoint concerns a specific rhythm-and-medication status. Neither type of information, absent comparative evidence and complete analysis reporting, establishes a causal effect. The value of the record is therefore in defining the study question and documenting selected design and safety information, while its missing results constrain 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 primary limitation for interpreting efficacy is that the registry record does not report the primary endpoint percentage or its 95% confidence interval. It also lists zero analyses, so no analysis-level efficacy estimate is available. The stated endpoint and the study's objective do not substitute for the missing numerical result.

The study is described as a single-group, non-randomized trial, with allocation not applicable and masking none. No randomized comparator is described. This limits causal and comparative interpretation, including comparisons with alternative treatments or usual care. The trial takes place during concomitant open cardiac surgery, so the registry record does not isolate the contribution of the device from other aspects of the surgical setting.

The primary analysis population is described as evaluable subjects, but the record does not give its size, a full definition of evaluability, or the primary analysis denominator. It also does not report how missing Holter assessments, deaths, or withdrawal were handled for the primary endpoint. The completer population excluded five subjects, with the reasons stated, but the relationship between that population and the primary efficacy analysis is not fully described.

The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, or a method for calculating the confidence interval. It lists assumptions for a planning illustration, but does not report resulting sample-size values or establish that those assumptions formed the trial's design. The record also does not provide the secondary efficacy results or the result for the composite major adverse event outcome.

For safety, the listed counts and event-term percentages do not by themselves establish causation or comparative risk. The record does not include further event-level details such as timing, relatedness, or duration in the summary. These limitations restrict interpretation to the information explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation — NCT00560885.
• Registry record last updated 2013-03-29; status last verified 2013-03.
• Results first posted 2013-03-14.
• 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

NCT00560885 is a completed Phase 3, prospective, non-randomized, multi-center, single-group trial of the AtriCure Bipolar System for permanent atrial fibrillation during concomitant on-pump cardiac surgery. Enrollment is listed as 55; the recorded start date is 2007-11 and primary completion date is 2009-12. Masking is listed as none.

The primary endpoint is the percentage of patients free from atrial fibrillation and off Class I and III anti-arrhythmic drugs at 6 months post procedure, assessed by Holter monitoring. The record specifies a 95% confidence interval but does not report the endpoint estimate or interval. It describes the primary analysis population as evaluable subjects and notes five exclusions from the completer population.

The safety summary lists 45 of 55 at risk as affected by serious adverse events and 51 of 55 at risk as affected by other adverse events. No primary efficacy analyses are listed. The registry record does not report a control-group comparison, a statistical analysis plan, or the primary efficacy result.