Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Longstanding Persistent Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Longstanding Persistent Atrial Fibrillation (NCT01558635), a na na study. The primary outcome is Efficacy: Percentage of Treated Subjects Diagnosed With Longstanding Persistent AF Off Class I or III Antiarrhythmic Drugs and Out of AF at 12 Months, and Who Did Not Receive Additional Ablation Therapy for AF Prior to the 12-month Evaluation..

2. Clinical Question

The endpoint combined several conditions: medication status, rhythm-monitor findings, and whether another ablation had occurred. It defined being out of AF using an AF burden <0.5% per 24h. Cardioversions were allowed only during the 12 week blanking period. Additional ablation could include percutaneous catheter ablation or AV nodal ablation.

This question concerns an outcome after a combined surgical setting: the ablation system was used alongside mitral valve surgery and a Maze III procedure. Because the registry lists only one group, its results cannot establish how outcomes compare with those under a different procedure or no ablation. The endpoint description states what counted as success, but the registry record does not report the achieved primary endpoint count or percentage.

3. Trial Design

The study, NCT01558635, evaluated the Cardioblate CryoFlex Surgical Ablation System in subjects with longstanding persistent atrial fibrillation requiring mitral valve surgery. The registry lists a single-group model, enrollment of 17, and allocation as NA. Masking is listed as NONE, and phase is listed as NA. The study status is TERMINATED.

The described group underwent a Maze III procedure using Cardioblate CryoFlex ablation concomitant to mitral valve surgery. A Medtronic Reveal XT Insertable Cardiac Monitor was implanted during surgery to monitor subsequent AF episodes. The intervention list also includes mitral valve surgery and MAZE III, reflecting that the ablation took place within a broader surgical procedure rather than as a standalone intervention.

The registry lists a start of 2011-11 and primary completion of 2016-01. It does not report why the study was terminated. The planned enrollment and the number with endpoint data are distinct: the registry says 17 subjects were enrolled, 11 had data at 12 months that included antiarrhythmic drug, ablation, and cardioversion information, and six had the AF-burden data required for the primary endpoint.

There is no randomized comparator group in the design described by the registry. Consequently, the study can describe outcomes in the treated group but cannot separate the effects of the ablation system from the effects of concurrent surgery, participant characteristics, or other influences. The registry record does not report a statistical analysis plan, a sample-size justification, or interim analyses.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: There were 11 subjects with data at 12 months, including antiarrhythmic drug, ablation, and cardioversion data. However, only six subjects had the AF burden data required for the primary efficacy endpoint.

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 Efficacy: Percentage of Treated Subjects Diagnosed With Longstanding Persistent AF Off Class I or III Antiarrhythmic Drugs and Out of AF at 12 Months, and Who Did Not Receive Additional Ablation Therapy for AF Prior to the 12-month Evaluation., measured over 12 months.

The primary endpoint was the percentage of treated subjects with longstanding persistent AF who, at 12 months, were off Class I or III antiarrhythmic drugs, out of AF on Reveal XT recordings, and had not received additional AF ablation before the 12-month evaluation. The threshold for being out of AF was AF burden <0.5% per 24h. Cardioversions were allowed only during the 12 week blanking period.

This is a composite success definition: a participant had to meet the medication, rhythm, and additional-treatment conditions together. It therefore captures more than a rhythm recording alone. The medication condition asks whether the rhythm status was maintained without the specified drug classes; the additional-ablation condition distinguishes outcomes achieved without another ablation procedure. The monitor-based burden threshold supplies the operational definition of out of AF.

Such a definition can be useful when a study aims to assess a clinically interpretable state after treatment rather than a single measurement in isolation. However, the components also mean that a participant could fail the endpoint for different reasons. The registry record reports six subjects with the AF-burden data required for this endpoint, but does not report the number meeting all its criteria or the resulting percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and lists no analyses. The statistical concepts below explain how such outcomes are commonly interpreted; they do not describe an analysis plan that is reported for this study.

What does the primary endpoint count?

The endpoint is binary at the participant level: each participant either satisfies every listed condition or does not. The conditions are being off Class I or III antiarrhythmic drugs, meeting the monitor-based AF-burden threshold at 12 months, and having no additional AF ablation before that evaluation. A percentage for this endpoint would be based on participants meeting all conditions relative to the relevant endpoint population. The registry gives the definition and says six subjects had the necessary AF-burden data, but does not state how many met all conditions or give the percentage.

Binary outcomes are often presented as counts and proportions because the result can be understood as the frequency of a specified state. Interpretation still depends on the denominator: participants without the required data cannot simply be assumed to have met or failed the endpoint. The record does not explain how missing measurements were handled or whether any imputation or sensitivity analysis was used.

Why do confidence intervals matter?

In general, a confidence interval describes the uncertainty around an estimated quantity under a statistical model. For a participant proportion, it helps show how much uncertainty remains when the estimate is based on a finite group. The interval's width depends in part on the amount of information available. An estimate alone does not show its precision; an interval can help readers distinguish a tightly estimated result from one with substantial uncertainty.

No primary endpoint confidence interval or numerical estimate is reported in the registry record. There is therefore no interval to interpret and no basis for describing the precision of an estimated success percentage. The small number of subjects with the required AF-burden data makes the limited endpoint availability especially important when considering how much information would be available even if an estimate were reported.

How should a single-group study be read?

A single-group study can describe what happened among participants who received the intervention, but does not directly estimate a contrast against a control group. A difference from a hypothetical alternative cannot be established from this design alone. Other influences, including concurrent procedures and participant characteristics, can contribute to outcomes. The registry describes ablation alongside mitral valve surgery and a Maze III procedure; the contributions of these components cannot be separated by a comparison within the stated design.

Allocation is listed as NA, and the registry identifies no randomized comparison. Masking is listed as NONE. These entries describe features of the registry record, but do not supply further detail about who assessed outcomes or how outcome assessments were conducted. The record does not report an analysis plan addressing potential sources of bias.

What can planning calculations tell readers?

In general, sample-size planning calculations estimate how many participants might be needed under specified assumptions about a target effect, variability, significance level, allocation, and analysis method. They are planning illustrations, not observed results and not a measure of the probability that a completed study found an effect. The illustrations associated with this study are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects defined as stated fractions of an observed effect. Time-to-event illustrations use a total number of events; other illustrations use participants per arm.

Those assumptions describe hypothetical planning, not the design reported for this single-group trial. The registry record does not report the study's own sample-size justification. A hypothetical two-arm calculation should not be read as evidence that the study had two arms, nor should it be read as an observed power calculation.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a model assumes. If a statistical model assumes less variation than is present, standard errors and uncertainty estimates can be too small, making results appear more precise than they are. The appropriate response depends on the outcome and the model. The registry record does not identify a statistical model for the trial outcomes, so it is not possible to assess whether over-dispersion was considered or relevant to any analysis.

Overall, statistical interpretation requires an outcome estimate, its denominator, and information about uncertainty and analysis choices. The record supplies an endpoint definition and limited data-availability information, but does not report the primary result, uncertainty estimates, or analysis details.

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("Cardioblate CryoFlex Surgical Ablation")
n      <- c(6)
events <- c(5)
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  Cardioblate CryoFlex Surgical Ablation  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, spanning AF outcomes, quality of life, and acute major adverse events. It also repeats the same freedom-from-AF outcome label. When a study assesses several outcomes or several time points, there can be multiple opportunities to observe an apparently notable result by chance. General statistical practice may address this through a prespecified hierarchy, adjustment, or careful emphasis on a primary outcome. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how multiple outcome assessments were accounted for.

The primary endpoint has a stated definition, but the record does not report its achieved count or percentage, a confidence interval, or a hypothesis test. It lists no analyses. No conclusions about statistical significance can therefore be drawn from the primary result in this record.

Missing endpoint data are material. There were 11 subjects with 12-month information on antiarrhythmic drug, ablation, and cardioversion data, but only six with the AF-burden information needed for the primary endpoint. The registry record does not report why AF-burden data were unavailable for the others, whether missingness was related to participant outcomes, or how missing data were treated. General statistical interpretation must account for the possibility that participants with observed data differ from those without it; the direction or size of any resulting bias cannot be determined from the record.

The record does not report the analysis population, an approach to missing data, sensitivity analyses, interim analyses, or a detailed statistical plan. These omissions limit assessment of how outcomes were selected and evaluated, and whether results could be sensitive to analytical choices.

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: pleural effusion (23.5%), respiratory failure (11.8%), cardiac failure (11.8%), rib fracture (11.8%), transient ischemic attack (5.9%).

The adverse-event record reports 17 participants at risk for serious adverse events, with 9 affected; it reports 17 at risk for other adverse events, with 3 affected. It also reports 1 death. These are counts in the study group, not comparisons with another group. The record does not establish that an event was caused by the ablation system or procedure simply by listing it.

The listed serious-event terms and percentages are Pleural Effusion, 23.5%; Respiratory Failure, 11.8%; Cardiac Failure, 11.8%; Rib Fracture, 11.8%; Transient Ischemic Attack, 5.9%; and Syncope, 5.9%. The registry record does not give counts alongside these term percentages in the registry record, or state whether participants could have more than one listed event. The term percentages should therefore not be added or treated as mutually exclusive categories.

The separate death count does not specify cause or relationship to treatment. Nor do the aggregate adverse-event counts describe event timing, duration, severity beyond the serious classification, or the number of events per participant. These figures provide a safety description for the treated group, but a single-group record cannot establish comparative risk.

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

The registry record identifies a relevant statistical question: whether participants met a combined 12-month endpoint after surgical ablation performed with mitral valve surgery. It specifies the rhythm threshold, medication condition, and restriction on additional ablation. It also indicates that only six subjects had the AF-burden data required to evaluate that endpoint.

The record does not report the number who met the endpoint or the percentage who did so. Thus it does not support a numerical statement about the observed primary outcome. There is also no reported confidence interval or analysis result to characterize uncertainty. The endpoint definition alone cannot be interpreted as an outcome finding.

Even if a treated-group outcome estimate were available, the single-group design would describe participants in this study rather than establish a comparative treatment effect. The registry does not include a control group against which outcomes can be compared. Since the procedure included mitral valve surgery and a Maze III procedure, the design also cannot isolate the contribution of the ablation system from the other components of care.

The enrollment of 17 and the smaller numbers with follow-up information and required AF-burden data matter for interpretation. The record does not explain the missing data or how they were handled. It is not possible to determine whether the subjects with available monitor data represent all enrolled subjects in ways relevant to the endpoint.

The safety counts describe events reported in the treated group. They do not demonstrate comparative safety, establish causation, or explain the reported death. The status TERMINATED is recorded, but the reason for termination is not reported in the registry record. Overall, the record documents the study question and some participation and safety information, while leaving the primary efficacy result and its statistical uncertainty unreported.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition, an endpoint result, and an analysis are different pieces of evidence. The registry specifies a combined definition for success at 12 months, including medication status, monitor-derived AF burden, and avoidance of additional ablation. Yet the record does not report the number or percentage meeting that definition. A clearly defined outcome cannot by itself answer whether participants achieved it.

It also illustrates why denominators need close attention. The record reports 17 enrolled subjects, 11 with certain 12-month information, and six with the AF-burden data required for the primary endpoint. These counts describe different levels of data availability. Treating all enrolled participants as though they had complete endpoint data would obscure the actual basis for evaluation.

The design is equally important. A single group can describe observed outcomes, but it cannot furnish a randomized treatment contrast. This matters in a combined surgical setting, where the ablation was performed with mitral valve surgery and a Maze III procedure. Without a comparator, treatment-specific effects cannot be distinguished from other influences.

Finally, the registry lists multiple outcome measures but no analyses. This highlights the value of prespecified analysis plans, transparent reporting of missing data, and uncertainty estimates. Those details allow readers to assess how outcomes were evaluated and how much confidence to place in numerical estimates. The available record states the clinical question and some safety information, but leaves key information needed for statistical interpretation unreported.

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 achieved primary endpoint count or percentage. Although the endpoint is defined and six subjects had the necessary AF-burden data, no estimate or uncertainty interval is reported. The outcome cannot be quantified from the information in the record.

Endpoint data were not available in the same numbers as enrollment: 17 subjects were enrolled, 11 had 12-month antiarrhythmic drug, ablation, and cardioversion data, and six had the required AF-burden data. The reasons for missing monitor data and the method used to handle missing outcomes are not reported. Any representativeness of the available endpoint data is therefore unknown.

The single-group design offers no concurrent randomized comparator. It cannot estimate a comparative effect or distinguish the contribution of the ablation system from mitral valve surgery and the Maze III procedure. Masking is listed as NONE, while details about outcome assessment procedures are not reported.

The registry lists 8 outcome measures and no analyses. It does not report how multiplicity was addressed, the statistical analysis plan, the analysis population, interim analyses, or the study's sample-size justification. The reason the study was terminated is also not reported in the registry record. These gaps restrict assessment of outcome selection, analytic choices, statistical precision, and the circumstances of study completion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Longstanding Persistent Atrial Fibrillation — NCT01558635.
• Registry record last updated 2019-07-30; status last verified 2019-07.
• Results first posted 2019-03-01.
• 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

NCT01558635 is a terminated, single-group study of Cardioblate CryoFlex Surgical Ablation in subjects with longstanding persistent AF requiring mitral valve surgery. Enrollment was 17. The listed procedure combined ablation with a Maze III procedure and mitral valve surgery, with a Reveal XT monitor implanted during surgery.

The primary endpoint assessed a combined 12-month outcome based on medication status, AF burden, and no additional AF ablation. The registry reports 11 subjects with specified 12-month information and six with the AF-burden data required for the primary endpoint, but does not report the achieved endpoint count or percentage. It lists 8 outcome measures and no analyses.

The record reports serious adverse events in 9 of 17 participants, other adverse events in 3 of 17, and 1 death. It does not report why the study was terminated, a comparator-group result, or a statistical analysis plan.