ABLATE Post Approval Study - Synergy Ablation Lesions for Non-Paroxysmal Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ABLATE Post Approval Study - Synergy Ablation Lesions for Non-Paroxysmal Atrial Fibrillation (NCT01694563), a na na study. The primary outcome is The Number of Participants Free From Atrial Fibrillation (AF), Atrial Flutter or Atrial Tachycardia While Off Class I and Class III Antiarrhythmic Drugs for at Least 4 Weeks..

2. Clinical Question

3. Trial Design

This was a completed, single-group post-approval registry study of the AtriCure Synergy Ablation System. The registry lists enrollment as 365 and gives the study start as 2012-09 and primary completion as 2017-10-23. Its stated objective was to evaluate clinical outcomes among patients with persistent or longstanding persistent atrial fibrillation treated during commercial use of the device by physicians performing the Maze IV procedure.

Eligible patients were described as scheduled for elective concomitant open, on-pump cardiac surgery and a Maze IV ablation procedure. The intervention was the Synergy Ablation System. There was no separate control arm: the record identifies a single-group design and lists allocation as not applicable. Masking is listed as none. These features mean the study is a follow-up of an intervention cohort, not a randomized comparison of treatment strategies.

The primary outcome concerns freedom from atrial fibrillation, atrial flutter, or atrial tachycardia off specified antiarrhythmic drugs at 36 months post-operatively. The detailed endpoint description specifies that the rhythm assessment used a 48-hour Holter, Zio Patch, or pacemaker interrogation recording, with assessment at a minimum of 36 months. The record also lists a secondary efficacy outcome, but its detailed definition and results are not reported in the registry record.

The registry lists the study phase as not applicable. A protocol, detailed statistical analysis plan, eligibility criteria beyond the summary description, and further information about follow-up procedures are not reported in the registry record. The record does not describe a concurrent comparator or a masking procedure.

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: Freedom from AF and off antiarrhythmic drugs (AADs) at specific time points. The participants that met the endpoint are reflected in the Outcome Measure Data Table.

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 The Number of Participants Free From Atrial Fibrillation (AF), Atrial Flutter or Atrial Tachycardia While Off Class I and Class III Antiarrhythmic Drugs for at Least 4 Weeks., measured over 36 months post-operatively.

The primary endpoint is a count of participants meeting a combined rhythm and medication criterion at 36 months post-operatively. A participant had to be free of atrial fibrillation, atrial flutter, and atrial tachycardia, with arrhythmia episodes defined as lasting >30 continuous seconds, while off Class I and Class III antiarrhythmic drugs for at least 4 weeks. The determination was based on the core laboratory’s last assessment of a 48-hour Holter, Zio Patch, or pacemaker interrogation recording performed at a minimum of 36 months post-operatively.

Combining rhythm status with medication use defines a particular clinical outcome rather than rhythm status alone. The endpoint therefore distinguishes participants meeting both conditions from those who do not meet the combined criterion. As a general statistical point, a clearly specified endpoint helps readers understand what event or state an analysis counts; it does not, by itself, establish how complete or precise the resulting estimate is.

The registry identifies the endpoint and its assessment approach, but does not report the number of participants who met it, the analysis denominator, or an uncertainty interval. Consequently, the posted results do not establish the observed frequency or precision of this primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study, with allocation listed as not applicable and masking as none. In a single-group design, outcomes are observed among participants receiving the intervention, rather than compared with outcomes in a separate randomized group. As a general statistical principle, this design can describe what happened in the cohort but cannot by itself separate the intervention’s contribution from other influences. It does not provide the protection against confounding that random allocation can offer.

What does the primary endpoint count?

The primary measure is a count of participants meeting a composite criterion. Participants had to be free from atrial fibrillation, atrial flutter, or atrial tachycardia, with an episode defined as lasting >30 continuous seconds, while off Class I and Class III antiarrhythmic drugs for at least 4 weeks. The registry specifies a core laboratory’s last assessment of a 48-hour Holter, Zio Patch, or pacemaker interrogation recording, performed at a minimum of 36 months post-operatively. This definition matters because the outcome is not simply a count of participants with a particular rhythm at any time; it combines rhythm findings, medication status, and a specified assessment time.

The record does not report the number meeting this definition or the denominator used for the primary analysis. It also does not report an uncertainty interval or the statistical method used for the primary endpoint. Without those details, readers cannot evaluate how precisely the observed endpoint was estimated or whether all enrolled participants contributed to the analysis.

How should a confidence interval be understood?

As a general explanation, a confidence interval describes statistical uncertainty around an estimated quantity under the assumptions of the method used to calculate it. An estimate with a wider interval is less precise than one with a narrower interval. Intervals are not reported for the primary endpoint in the registry record, so its precision cannot be judged from an interval. A count without its analysis denominator is also insufficient to establish the endpoint frequency.

What do the sample-size assumptions represent?

The record describes sample-size calculations as planning illustrations based on an observed effect, not as the study’s own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. The record says that time-to-event illustrations use a total event count, while other illustrations use participants per arm.

These assumptions describe hypothetical planning comparisons, even though the study itself is single-group. They should not be read as the number enrolled, as evidence that a particular statistical power was achieved, or as proof that the original study was designed around those calculations. The actual sample-size justification and statistical plan are not reported in the registry record. No numerical sample-size illustration is described in the registry entries, so no such value can be interpreted.

Why can adverse event counts overlap?

As a general point, one participant may experience more than one adverse event, and a participant may appear in more than one event category. Thus, counts across event types should not automatically be added to produce a total number of affected participants. The registry gives separate at-risk and affected counts for serious and other adverse events, but does not provide a detailed account of whether or how the categories overlap. Adverse event counts also do not establish causation: an event recorded during follow-up is not necessarily caused by the device or procedure.

What analysis details are absent?

The record lists two outcome measures and four analyses, but does not report the specific analysis methods or the detailed results of the secondary efficacy outcome. The statistical plan, any adjustments, interim analyses, missing-data methods, and analysis populations are not reported in the registry record. These omissions limit assessment of how the results were selected, calculated, and handled when observations were unavailable.

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("36 Months Post-operatively")
n      <- c(232)
events <- c(146)
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  36 Months Post-operatively  232  146  62.9  56.4  69.2  56.6  68.9  56.5  68.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and four analyses. The details available do not identify the four analyses, explain how they relate to the listed measures, or state whether any adjustment for multiple statistical tests was planned or used. Multiplicity is a general concern when several outcomes or analyses are examined: more opportunities to find an apparently notable result can affect interpretation if the analysis strategy is not prespecified. The statistical plan and multiplicity approach are not reported in the registry record, so it is not possible to determine how this issue was handled.

The primary endpoint definition specifies a recording assessed at a minimum of 36 months post-operatively, but the record does not report the number of participants with an available assessment, the denominator used, or how missing recordings or incomplete follow-up were treated. Missing-data methods, reasons for missingness, and sensitivity analyses are not reported in the registry record. As a general statistical matter, missing outcomes can affect an estimate when the availability of measurements is related to participants’ outcomes or characteristics; the direction and extent of any such effect cannot be determined without further information.

The record does not describe an intention-to-treat, per-protocol, or other named analysis population for the primary endpoint. It also does not report whether the primary analysis included everyone enrolled or only those with an evaluable recording. The reported enrollment is 365, but that figure alone does not identify the analysis denominator. These omissions prevent a full assessment of the endpoint’s completeness and analytic population.

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: cardiac failure (24.7%), respiratory failure (17.8%), atrial fibrillation (12.3%), pleural effusion (11.0%), pneumonia (9.9%).

The registry lists 365 participants at risk in both its serious and other adverse event summaries. It reports 289 participants with serious adverse events, 271 with other adverse events, and 20 deaths. The listed serious adverse event terms include Cardiac Failure at 24.7%, Respiratory failure at 17.8%, Atrial Fibrillation at 12.3%, Pleural effusion at 11.0%, Pneumonia at 9.9%, and Renal failure at 8.8%.

These figures are descriptive safety data, not a comparison with an untreated or alternative-treatment group. The listed terms and percentages do not show whether an event was caused by the device, ablation procedure, underlying illness, or another factor. The registry record does not report the denominator or calculation basis for the term percentages, or the timing and causes of the deaths.

Serious and other adverse event counts should not be added: the record does not establish that the categories are mutually exclusive, and a participant may have more than one event. General statistical interpretation also distinguishes the number of participants with an event from the number of events themselves. The registry reports participant counts for the broad summaries, while its listed terms are presented as percentages.

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

The registry record describes a post-approval study of the Synergy Ablation System in patients with non-paroxysmal atrial fibrillation undergoing concomitant on-pump cardiac surgery and a Maze IV procedure. It identifies a specific primary outcome and reports safety summaries. These data provide a description of the study setting, planned endpoint, and recorded adverse events.

The primary efficacy result is not reported in the registry record. The number of participants meeting the endpoint, the analysis denominator, and any estimate of uncertainty are absent. Therefore, the posted information does not show how often participants were free from the specified arrhythmias while off the specified drugs at the assessment time, nor how precisely that outcome was estimated.

The single-group design does not include a randomized comparator. For that reason, the record cannot establish a difference in outcomes versus another treatment or establish that the device caused an observed outcome. More generally, clinical outcomes after a combined operation may reflect multiple factors; the record does not provide a comparative design that separates those influences.

The adverse event counts and listed terms describe events recorded in the study, but do not establish causation. The record does not report the causes or timing of deaths or the basis for the percentages listed for serious event terms. These limitations apply alongside the absence of a detailed statistical plan, missing-data methods, and analysis population definitions.

The registry’s planning assumptions are described as illustrations, not as the study’s own design or as observed power. Taken together, the record supports a limited descriptive reading of the cohort and its reported safety information, but does not support a quantitative conclusion about the primary efficacy outcome or a controlled treatment comparison.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a post-approval single-group registry and a randomized comparative trial. A registry can document outcomes in clinical use and define how an endpoint is assessed. Here, the record identifies a cohort undergoing Maze IV surgery with the Synergy Ablation System and specifies a rhythm-and-medication endpoint at 36 months post-operatively. That setting is relevant to understanding what the study intended to monitor.

Statistically, however, endpoint definition and endpoint results are separate. The record gives a detailed definition for the primary measure but does not report the number meeting it, the analysis denominator, or an uncertainty estimate. Without those results, the primary outcome cannot be judged for magnitude or precision from the registry record. This is a useful reminder that registration details alone do not necessarily provide the evidence needed to evaluate an outcome estimate.

The design also shapes what can be concluded. Because the study has one group and no randomized comparator, its observations cannot establish a comparative treatment effect. That limitation does not make descriptive information meaningless; it clarifies that the results answer a different kind of question. Safety summaries likewise describe recorded events but do not establish that the device or procedure caused them.

The record’s planning illustrations provide another statistical distinction: assumptions for hypothetical sample-size planning are not the same as the study’s design, and they are not observed power. Finally, the lack of reported missing-data methods, analysis populations, and multiplicity handling limits assessment of how complete and prespecified the outcome analyses were. These design and reporting features are central to interpreting the registry conservatively.

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 principal limitation for interpreting efficacy is that the registry does not report the primary endpoint result. The endpoint definition is detailed, but the number meeting it, analysis denominator, and uncertainty estimate are not reported in the registry record. The secondary efficacy outcome is listed without its detailed result.

The study is single-group, with no separate comparator, allocation listed as not applicable, and masking listed as none. Its design therefore does not provide a randomized estimate of the difference between treatment strategies. The record also does not report the statistical analysis plan, the analysis populations, the treatment of missing assessments, or any sensitivity analyses. These details would be needed to assess how the primary result was calculated and how incomplete follow-up was handled.

The primary endpoint depends on rhythm monitoring and medication status at a specified post-operative time. The registry describes acceptable recording sources and an assessment at a minimum of 36 months post-operatively, but does not report how many participants had an evaluable recording or whether recording methods differed across participants. The number with missing or incomplete endpoint information is not reported in the registry record.

For safety interpretation, the record reports participant counts and named serious event terms, but not the cause or timing of deaths or the basis for the term percentages. It does not establish whether events were related to the device or procedure. The record also lists planning assumptions for hypothetical sample-size illustrations, while the study’s own sample-size justification is not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ABLATE Post Approval Study - Synergy Ablation Lesions for Non-Paroxysmal Atrial Fibrillation — NCT01694563.
• Registry record last updated 2019-10-09; status last verified 2018-03.
• Results first posted 2019-09-13.
• 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 completed, single-group post-approval study of the AtriCure Synergy Ablation System during Maze IV surgery for persistent or longstanding persistent atrial fibrillation. Enrollment is listed as 365. Allocation is not applicable, masking is none, and phase is listed as not applicable.

The primary endpoint counts participants free from atrial fibrillation, atrial flutter, or atrial tachycardia while off Class I and Class III antiarrhythmic drugs for at least 4 weeks, based on rhythm assessment at a minimum of 36 months post-operatively. The primary endpoint result and its analysis denominator are not reported in the registry record.

The safety summary reports 289 participants with serious adverse events, 271 with other adverse events, and 20 deaths. The study has no separate control group, and the record does not report detailed methods for missing data, multiplicity, or the analysis population.