PV-Isolation With the Cryoballoon Versus RF:a Randomized Controlled Prospective Non-inferiority Trial (FreezeAF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PV-Isolation With the Cryoballoon Versus RF:a Randomized Controlled Prospective Non-inferiority Trial (FreezeAF) (NCT00774566), a randomized phase 4 study. The primary outcome is Combined Endpoint Out of: Absence of Atrial Arrhythmias and Absence of Persistent Complications at Six Months After the Index Procedure.

2. Clinical Question

The trial therefore addresses a comparison between two procedural approaches in a defined clinical context, rather than a comparison with no ablation. Its primary outcome combines an efficacy component, absence of atrial arrhythmias, with a safety-related component, absence of persistent complications. A participant had to meet both components to count toward the combined endpoint as described in the record.

The registry also names procedural complications and other measures for comparison, including pain scores during the procedure, cardiac inflammatory markers, short- and long-term clinical success, and costs. The primary result should be interpreted according to its stated combined definition; it does not by itself describe each component separately. Separate component results are not reported in the registry record.

3. Trial Design

The registry describes FreezeAF as a randomized, controlled, prospective, non-inferiority trial with a parallel-group design. It is listed as phase 4, with no masking. The study status is completed. The listed enrollment is 322.

The treatment groups were radiofrequency ablation and cryoballoon ablation. The radiofrequency group used segmental pulmonary vein isolation with an irrigated-tip catheter, while the cryoballoon group used pulmonary vein isolation with a cryoballoon. The registry describes the comparison as isolation of the pulmonary veins for treatment of paroxysmal atrial fibrillation.

The registry lists the study start as 2008-10 and primary completion as 2014-12. It identifies Städtisches Klinikum Karlsruhe as the sponsor. The record does not report the method used to generate the random allocation sequence, allocation concealment, or how outcome assessment was handled in the absence of masking. Details of the protocol and participant flow are not reported in the registry record.

The primary endpoint was assessed six months after the procedure. The record describes a restriction on redo procedures: they were allowed only after the six-month follow-up and had to use the same energy source. It also states that no ADD administration was allowed after ablation; the meaning of the abbreviation is not reported in the registry record. These details matter to understanding the recorded endpoint and follow-up, but do not replace a complete analysis plan.

The registry lists secondary outcomes that include mid-term and long-term clinical success, total radiation exposure, total procedure duration, and major adverse events. Five secondary outcomes are posted, while the registry lists seven outcome measures overall. Further details about allocation implementation, follow-up completeness, and analysis populations are not reported in the registry record.

4. Participant Flow and Accounting

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

Before assignment: A total of 322 patients were included, with 7 not receiving treatment as part of the trial because of a withdrawal of consent but without knowing group assignment leaving 315 patients randomly assigned. This resulted in a final ITT population of 315 patients.

Overall Study

Reasons for not completing this period:

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 Combined Endpoint Out of: Absence of Atrial Arrhythmias and Absence of Persistent Complications at Six Months After the Index Procedure, measured over Six months after procedure.

The primary endpoint is a combined measure assessed six months after the procedure. It counts participants meeting both stated conditions: absence of atrial arrhythmias and absence of persistent complications. The endpoint therefore brings together a clinical success criterion and a persistent-complication criterion in one outcome.

A combined endpoint can capture more than one aspect of a treatment’s performance and may represent a broader study question than either component alone. Its interpretation depends on the precise components, their definitions, and the rules used to determine whether a participant meets each one. Here, the registry gives the overall combined definition but does not report separate component counts or detailed operational definitions for atrial arrhythmias and persistent complications.

The posted counts are 99 participants in the RF Ablation group and 98 in the CB Ablation group. The corresponding outcome denominators are 154 and 150. These outcome counts and denominators are the basis for the posted comparison; they are not a substitute for information about participant flow or missing outcome data, which is not reported in the registry record.

The endpoint is relevant to the trial’s stated non-inferiority question because it was designated as the primary outcome for comparing the procedures. However, a combined endpoint result alone does not establish that each component had a similar pattern. The non-inferiority margin and the prespecified statistical decision rule are not reported in the registry record, so the posted result cannot be interpreted as a formal demonstration of non-inferiority from the available information.

7. Results Posted in the Registry

• CB Ablation: 65.3% (98/150) versus 64.3% (99/154) on control; risk difference 1.0 percentage points (95% CI -9.7 to 11.8), risk ratio 1.02 (0.86–1.20); unadjusted two-proportion z-test p = 0.848.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Long-term Clinical Success

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CB Ablation: 90.4% (141/156) versus 88.7% (141/159) on control; risk difference 1.7 percentage points (95% CI -5.1 to 8.5), risk ratio 1.02 (0.95–1.10); unadjusted two-proportion z-test p = 0.621.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CB Ablation and the control. The interval gives the range of effects that remain compatible with the data.

Mid-term Clinical Success

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CB Ablation: 96.2% (150/156) versus 96.9% (154/159) on control; risk difference -0.7 percentage points (95% CI -4.8 to 3.4), risk ratio 0.99 (0.95–1.04); unadjusted two-proportion z-test p = 0.735.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CB Ablation and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists five posted secondary outcomes, including clinical-success outcomes at mid-term and long-term follow-up, as well as radiation exposure, procedure duration, and major adverse events. The outcome list is broader than the primary combined endpoint, but the record does not give full definitions or posted comparative results for every listed measure. The analyses for the secondary outcomes are not reported in the registry record.

The clinical-success results provide context for the primary six-month combined endpoint, but they should not be treated as repeated measurements of precisely the same outcome. The primary endpoint explicitly combines absence of atrial arrhythmias with absence of persistent complications. The secondary clinical-success titles do not establish that they use the same component definitions. The long-term outcome is listed at twelve months, while the mid-term outcome is listed at six months.

Across the posted secondary comparisons, the point estimates do not all point in the same direction, and the intervals include zero. This overall pattern does not settle the primary non-inferiority question. A secondary endpoint can support interpretation when its definition, analysis, and relationship to the primary endpoint are clear, but it cannot replace the prespecified primary analysis.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities for chance findings. Without a reported multiplicity plan, a nominal p-value should not be treated as a definitive confirmatory result. The record also does not report a hierarchy or testing sequence that would establish which secondary outcomes were intended to support formal claims. These results are best considered descriptive context, with the primary endpoint and its uncertainty remaining central.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Long-term Clinical Success
• Total Radiation Exposure
• Total Procedure Duration
• Major Adverse Events
• Mid-term Clinical Success

9. Statistical Interpretation

10. Statistical Methods Explained

A randomized comparison aims to make treatment groups comparable, on average, by assigning participants to groups through chance. Randomization supports a causal comparison when it is properly implemented and when subsequent follow-up and analysis preserve the benefits of that assignment. The registry identifies the study as randomized, but does not report sequence generation or allocation concealment. Those details are not reported in the registry record.

What does the risk difference describe?

The risk difference expresses the difference between the proportions meeting the endpoint in the two groups. The posted comparison uses CB Ablation minus RF Ablation, so a positive estimate means the observed proportion was higher in the CB group, while a negative estimate means it was lower. The primary estimate is 0.011. This is an unadjusted comparison based on the posted summary counts, not an adjusted model result.

A risk difference is often useful because it stays on the scale of absolute group separation. It can be interpreted alongside the endpoint’s definition and the confidence interval. It does not, by itself, explain why the groups differ, account for unmeasured factors, or establish that a small observed difference is clinically unimportant.

What does the confidence interval add?

A confidence interval expresses the uncertainty around an estimated effect under the statistical method used. In repeated sampling, a method that constructs 95% confidence intervals would capture the underlying effect in 95% of samples under its assumptions. For an individual study, the interval is a range of effect values compatible with the data and method; it is not a guarantee that the true effect lies within that specific range.

For the primary comparison, the 95% confidence interval runs from -0.097 to 0.118. Because it includes zero, the data are compatible with no difference as well as with differences in either direction. Its width indicates that the estimate is not highly precise. Whether that range is sufficiently narrow for the trial’s non-inferiority question depends on the prespecified margin, which is not reported in the registry record.

What does the p-value say?

An unadjusted p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the statistical model’s assumptions were true. It is not the probability that the null hypothesis is true, the probability that the result occurred by chance, or a measure of clinical importance. The primary unadjusted p-value is 0.848. That value does not prove the groups are equivalent and does not replace the confidence interval or a non-inferiority decision rule.

The registry reports no analyses for the outcomes, so the displayed comparisons are not accompanied by a reported model specification, covariate adjustment, or detailed inferential procedure. The risk differences and their intervals are simple unadjusted re-calculations from posted summary statistics. The discrepancy flag is false, so no conflict with a separate sponsor analysis is identified in the record.

Why does non-inferiority need a margin?

A non-inferiority trial asks whether the experimental procedure is not worse than the comparator by more than a prespecified amount. The margin marks the largest disadvantage that would still be accepted for the trial’s purpose. A conclusion depends on both that margin and the confidence interval’s position relative to it, alongside the prespecified analysis approach. Without the margin, the observed estimate and interval cannot answer the formal non-inferiority question. The registry record does not report the margin, sample-size justification, or the original statistical plan.

Why might analyses of a binary endpoint use different methods?

The primary outcome is binary at the participant level: each participant either meets the combined endpoint or does not, according to the study definition. Statistical methods for binary outcomes can compare proportions, risk differences, risk ratios, or odds ratios. These measures describe the same data on different scales and can give different impressions of magnitude. The posted primary comparison emphasizes the risk difference; the record also lists a risk ratio and an odds ratio with their intervals. No adjusted analysis is reported.

General statistical methods may also account for clustering, repeated observations, or other departures from simple independent binary observations when the design requires them. Such methods should not be presumed to have been used in this trial: the registry does not report them. Over-dispersion is a general concern when variability exceeds what a chosen model expects; allowing for it can prevent uncertainty from being understated. The available record does not indicate that over-dispersion was relevant or that a model addressing it was used.

How should secondary comparisons be treated?

Secondary outcomes can broaden the description of a trial, but multiple comparisons increase the chance of at least one apparently notable result even when there is no underlying effect. A prespecified multiplicity strategy can control or otherwise address that issue. The registry does not report such a strategy. The secondary p-values are unadjusted, and the record lists no reported analyses. They are most appropriately treated as exploratory or descriptive rather than as independent confirmatory evidence.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.011, and its 95% confidence interval extends from -0.097 to 0.118. The interval includes zero, so the result does not isolate a direction of difference. It also spans values that could represent a meaningful difference in either direction, depending on the clinical context and the non-inferiority margin. That margin is not reported in the registry record.

Precision concerns how narrowly the data locate the effect, not whether the point estimate looks close to zero. A point estimate near zero can still be uncertain when the interval is wide. Conversely, a narrow interval can provide relatively precise information even when the point estimate is not zero. Here, the interval’s breadth means that the study result is compatible with more than one interpretation of the between-group difference.

The secondary clinical-success comparisons have confidence intervals that also include zero: the long-term risk difference is 0.017, with an interval from -0.051 to 0.085, and the mid-term risk difference is -0.007, with an interval from -0.048 to 0.034. These are distinct outcomes and timeframes; they should not be treated as substitutes for the primary combined endpoint.

Confidence intervals reflect sampling uncertainty under the method used, not every source of uncertainty. They do not account automatically for missing outcomes, measurement limitations, selective reporting, or deviations from the intended analysis. Details needed to assess those issues are not reported in the registry record. The intervals therefore help describe statistical precision, but cannot resolve limitations in the reporting or establish the trial’s non-inferiority conclusion.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations describe hypothetical future planning based on the observed effect, not the trial’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The binary-outcome planning figures are participants per arm, not total participants or total events. For the primary endpoint, planning for 100% of the observed effect corresponds to 32,620 participants per arm for 80% power and 43,668 participants per arm for 90% power. Planning for 75% of the observed effect corresponds to 58,090 participants per arm for 80% power and 77,765 participants per arm for 90% power. Planning for 50% of the observed effect corresponds to 130,922 participants per arm for 80% power and 175,267 participants per arm for 90% power.

The 80% power column represents the planned chance of detecting the specified effect under the stated assumptions if that effect is the true one; the 90% column uses a higher target chance of detection. Higher power generally requires more participants. The illustrations also show that smaller effects need more participants, because smaller group differences are harder to distinguish from random variation.

These are planning illustrations, not observed power. They should not be read as evidence that the completed trial had a particular probability of finding an effect, nor as a retrospective judgment of study quality. The figures depend on the observed effect, which is uncertain, and on planning assumptions that may not match a real future study. Other binary endpoints have their own corresponding planning illustrations.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.643; treatment proportion p₁ = 0.653; average p̄ = 0.648.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6754 = 1.3237.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6753 = 0.5684.
4. n = (1.3237 + 0.5684)² / (0.0105)² = 32,619.6, rounded up to 32,620 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.642857142857143                          # control proportion
p1 <- 0.653333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(774566)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 32,620 (80% power), 43,668 (90% power)
 75% of observed effect: n per arm = 58,090 (80% power), 77,765 (90% power)
 50% of observed effect: n per arm = 130,922 (80% power), 175,267 (90% power)
power.prop.test: 32619.6 
Simulated power at n = 32,620 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, comparison, time point, or analysis. As the number of statistical tests grows, the chance of observing an apparently unusual result by chance can increase. Researchers may address this through a prespecified strategy, such as adjusting inference, defining an outcome hierarchy, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy or testing hierarchy.

The trial has a stated primary endpoint and multiple secondary outcomes, with clinical success assessed at more than one timeframe. The registry lists seven outcome measures overall and five posted secondary outcomes. The posted secondary comparisons have unadjusted p-values, and no reported analyses are listed. Without further documentation, the secondary p-values should not be interpreted as multiplicity-adjusted evidence.

Missing-data handling is also important because the outcome denominators differ from the enrollment figure, and the record does not explain participant flow or why the outcome denominators take the posted values. The primary endpoint counts use denominators of 154 for RF Ablation and 150 for CB Ablation. The secondary outcomes use their own posted denominators. These registry entries alone do not identify who lacked an outcome assessment, how missingness was handled, or whether the analyses followed intention-to-treat or per-protocol principles.

Analysis populations are particularly relevant in a non-inferiority trial. Different populations can lead to different estimates, and the protocol usually defines which analyses are central to the non-inferiority conclusion. The registry does not report an intention-to-treat population, a per-protocol population, or how deviations from assigned treatment were handled. It also does not report sensitivity analyses for missing outcomes or protocol deviations.

The record does not report the original statistical analysis plan, interim analyses, or sample-size justification. Those omissions limit assessment of whether the posted endpoints, analyses, and decision rules match the prespecified plan. In particular, the non-inferiority margin and the formal decision criterion are unavailable. These gaps do not negate the posted counts, but they constrain what conclusions can be drawn from them.

15. 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: vascular complication (3.2%), phrenic nerve palsy (1.3%), pericardial effusion (1.3%).

The registry records serious adverse events among 159 participants at risk in the RF Ablation group and 156 participants at risk in the CB Ablation group. It lists 4 serious adverse events for RF Ablation and 9 for CB Ablation. Other adverse events are listed for 3 and 8 participants, respectively. The death count is 0 in each group.

These are descriptive counts from the registry record. They should be read with the stated at-risk denominators and not as a formal comparison of safety. The record does not provide a statistical analysis of adverse events, clarify whether the counts refer to participants or event episodes beyond the field’s description, or give detailed definitions and severity criteria. It also does not report the completeness of safety follow-up.

The registry lists vascular complication at 3.2%, phrenic nerve palsy at 1.3%, and pericardial effusion at 1.3% among the top serious adverse event terms. The record does not specify a group attribution for these listed percentages in the available safety summary. The counts and terms describe reported events; they do not establish a causal explanation or a definitive difference in safety between procedures.

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

The posted primary result describes a small estimated risk difference between the groups, with the estimate favoring CB Ablation on the stated CB-minus-RF scale. Its 95% confidence interval includes zero and extends in both directions. The result therefore does not precisely determine whether the combined endpoint was more common in one group, or how large any difference might be.

This is not the same as showing that the procedures are equivalent. Equivalence requires a prespecified range of differences considered acceptably similar and evidence that the uncertainty falls within that range. Nor does the result alone establish non-inferiority. A non-inferiority claim requires a defined margin and a prespecified decision rule; the registry record does not report either one.

The endpoint itself is a combined measure. The posted result does not show how the arrhythmia component and persistent-complication component behaved separately, because separate component results are not reported in the registry record. It also does not establish results for outcomes that were not posted or fully defined. Clinical outcomes, procedure characteristics, costs, and safety are related but distinct questions.

The randomized design is a strength for comparing groups, but a complete interpretation also depends on how randomization was implemented, how outcomes were followed, and which analysis populations were used. Those details are not reported in the registry record. The difference between enrollment and outcome denominators cannot by itself explain missingness or determine whether any bias resulted.

Accordingly, the available result supports a cautious description of the observed endpoint counts and their statistical uncertainty. It does not establish a formal non-inferiority conclusion, prove the absence of a clinically important difference, or provide medical advice about choosing a procedure. Interpretation should remain tied to the registry’s reported endpoint and the limitations of its record.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a randomized comparison with a non-inferiority objective. A non-inferiority design is not interpreted simply by asking whether a conventional test finds a statistically significant difference. It depends on a clinically justified margin, a prespecified decision rule, and an interval estimate that can be compared with that margin. The registry record does not report the margin, making the formal objective difficult to assess from the posted result alone.

The primary estimate is close to zero, while its confidence interval includes both negative and positive values. That contrast illustrates why point estimates should not be interpreted without their precision. A small observed difference does not establish that the true difference is small, and a non-significant result does not establish equivalence. Interval estimation makes the range of uncertainty visible.

The combined endpoint also highlights a design and interpretation issue: a composite can summarize more than one clinical dimension, but an overall result can conceal different patterns in its components. Separate results are not reported in the registry record. Readers therefore cannot determine from the primary count alone whether both components contributed similarly to the outcome.

Finally, the trial illustrates how registry reporting affects statistical interpretation. The record provides randomized design information, outcome counts, group comparisons, and secondary measures, but does not report the original analysis plan, missing-data methods, analysis populations, multiplicity approach, or non-inferiority margin. Recognizing those limits is part of interpreting evidence responsibly, not a substitute for examining the posted estimates.

18. 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.

Several limitations are specific to the information in this registry record. The non-inferiority margin and formal decision rule are not reported, so the stated trial objective cannot be evaluated against its intended threshold. The original sample-size justification and statistical plan are also not reported; the planning illustrations based on observed effects do not fill that gap.

The registry does not report the randomization sequence method, allocation concealment, detailed participant flow, or the handling of missing outcome data. It gives outcome denominators, but does not explain how those analysis populations were formed. Intention-to-treat and per-protocol results are not reported, which is particularly relevant when assessing a non-inferiority objective.

The primary outcome is composite, but component-specific counts and detailed definitions are not reported. The registry also does not report a multiplicity strategy for the several secondary outcomes and timeframes. Secondary analyses are listed without reported analyses, limiting assessment of their methods and confirmatory status.

Safety reporting is descriptive in the available record. Detailed event definitions, group attribution for the listed serious-event terms, and a formal between-group safety analysis are not reported. These limitations constrain conclusions about the procedures and should be distinguished from the information that is directly posted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: PV-Isolation With the Cryoballoon Versus RF:a Randomized Controlled Prospective Non-inferiority Trial (FreezeAF) — NCT00774566.
• Registry record last updated 2021-04-06; status last verified 2021-03.
• Results first posted 2021-04-06.
• 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.

22. Record Summary

FreezeAF is listed as a completed, phase 4, randomized, prospective, controlled, parallel-group trial with no masking. It compared radiofrequency segmental pulmonary vein isolation using an irrigated-tip catheter with cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation. The registry lists enrollment of 322, a start of 2008-10, and primary completion at 2014-12.

The primary endpoint was the combined outcome of absence of atrial arrhythmias and absence of persistent complications six months after the procedure. The posted risk difference for CB Ablation minus RF Ablation is 0.011, with a 95% confidence interval from -0.097 to 0.118 and an unadjusted p-value of 0.848. The interval includes zero, and the non-inferiority margin is not reported in the registry record.

Secondary clinical-success comparisons and descriptive adverse-event counts are also posted. Missing-data methods, analysis populations, multiplicity handling, and the original statistical plan are not reported in the registry record.