CryoCath Freezor CryoAblation Catheter System (CRYOFACTS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CryoCath Freezor CryoAblation Catheter System (CRYOFACTS) (NCT00621621), a non-randomized phase 4 study. The primary outcome is Device or Procedure Related AV Block Persistent Through Discharge From Hospital..

2. Clinical Question

3. Trial Design

CRYOFACTS is listed as a Phase 4, completed, post-approval study sponsored by Medtronic Cardiac Rhythm and Heart Failure. The registry record gives a start date of 2006-12 and a primary completion date of 2013-12. Enrollment is listed as 105. The intervention is the Freezor Cardiac Cryoablation Catheter CryoConsole System, used to deliver cryoablation for AVNRT.

The design is identified as non-randomized, unmasked, and single-group. The record also includes an external-data arm based on peer-reviewed published reports of adults treated with the Freezor catheter for AVNRT. Because those data are external rather than a concurrently randomized control group, the two arms should not be treated as if participants had been assigned to comparable groups under the same study conditions. Differences in populations, follow-up, or data collection could affect comparisons; the extent of such differences is not reported in the registry record.

The primary endpoint timeframe is stated as after 250 subjects have been enrolled, whereas listed enrollment is 105. The record does not explain this difference or state whether the endpoint was assessed at another time. It also does not report the protocol’s sample-size justification, recruitment details, interim analyses, or a statistical analysis plan. The study status is completed, but that status alone does not supply the missing primary endpoint findings or explain how completion related to the stated endpoint timeframe.

The registry record lists two outcome measures and no analysis records. The primary outcome concerns persistent device- or procedure-related atrioventricular block through hospital discharge. A secondary outcome concerns atrioventricular block requiring insertion of a permanent pacemaker during defined study follow-up. The length and schedule of that follow-up 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.

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.

Population: A total of 105 subjects gave actual consent in the study. Of the 105 consented 75 went on to have an ablation procedure performed. Data from 675 subjects were taken from published data that met inclusion criteria with publication search approved by the FDA.

6. Primary Endpoint

The registry lists the primary outcome as Device or Procedure Related AV Block Persistent Through Discharge From Hospital., measured over After 250 subjects have been enrolled..

The primary endpoint counts participants with device- or procedure-related atrioventricular block that persists through discharge from hospital. It is a binary participant-level outcome: a participant either meets the stated event definition or does not. The registry record specifies that the result is to be reported as a number of participants and gives a 95% confidence interval as the dispersion measure. The stated timeframe is after 250 subjects have been enrolled.

This endpoint focuses on a complication that persists through a defined point in the hospital course, rather than any transient block or any block observed at any time. In general, a clearly defined endpoint makes it easier to interpret what event is being counted and when it is assessed. A confidence interval helps describe the precision of an estimated event frequency: narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. This general interpretation does not establish whether the estimate is unbiased or clinically important.

The registry record does not report the primary endpoint count or its confidence interval. Consequently, the event frequency and the precision of its estimate cannot be assessed from the endpoint information alone. The secondary outcome is atrioventricular block requiring permanent pacemaker insertion during defined follow-up, but the follow-up duration and its result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a participant count and specifies a 95% confidence interval. It does not report an analysis method, a primary estimate, or a confidence interval. No analysis records are listed. The methods below explain, in general terms, how these quantities are commonly interpreted; they should not be read as a description of methods confirmed for this study.

What does a participant count represent?

For a binary endpoint, each participant is classified according to whether the defined event occurred. The count of participants with the event is a numerator, and the number evaluated for that endpoint is needed to interpret the count as a frequency. The registry’s endpoint is specifically persistent device- or procedure-related atrioventricular block through hospital discharge. The posted record does not give the endpoint numerator or the denominator used for its analysis. Enrollment is not automatically the same as the number assessed for a particular outcome: eligibility, availability of follow-up, or analysis-population definitions can affect that number. The applicable analysis population is not reported in the registry record.

How should a confidence interval be read?

In general, a confidence interval describes uncertainty around an estimate under the assumptions of the statistical method used. It is not a guarantee that the true value lies within the interval, and it does not address all sources of bias. A narrower interval generally indicates greater statistical precision, while a wider interval indicates less precision. The registry specifies a 95% confidence interval for the primary count, but no interval is reported. Its width and the precision it would convey therefore cannot be evaluated.

For a binary endpoint, an interval might accompany an estimated event proportion, but the registry describes the primary result as a number of participants. The reported endpoint value and the denominator would be needed to understand the scale of the result. Neither the estimate nor its interval should be reconstructed from unrelated enrollment or safety entries. The registry does not state whether the confidence interval would be exact, based on a normal approximation, or calculated by another method.

What does the non-randomized design imply?

In general, random allocation helps balance measured and unmeasured participant characteristics between study groups on average. This study is listed as non-randomized and single-group, and its external-data arm comes from published reports. An external comparator can provide context, but comparability depends on consistent participant selection, endpoint definitions, procedures, follow-up, and reporting. The registry record does not provide enough detail to establish whether those conditions were met. Any apparent difference between the in-study group and external data could reflect differences in the groups or in how data were collected, rather than an intervention effect.

There is no masking. In general, masking can reduce the influence of knowledge about intervention or study assignment on some outcome assessments and decisions. The importance of masking depends on the outcome and assessment process. The record does not describe an assessment process or state whether any safeguards were used to limit assessment bias. It would therefore be speculative to describe how lack of masking affected the endpoint.

What do the planning assumptions mean?

The record includes a planning illustration based on the observed effect, rather than a statement of the trial’s original design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is framed as a stated fraction of the observed effect. Such assumptions describe a hypothetical planning exercise, not the study’s observed statistical power. The actual calculated planning values are not reported among the registry entries available for interpretation, and the protocol’s own sample-size justification is not reported in the registry record.

In general, a significance level is a threshold used in a hypothesis-testing procedure, while power is the probability of detecting an effect of a specified size under the assumptions of that calculation. A planning illustration asks what sample size might be needed for a chosen effect and design assumptions. It cannot establish how much power the completed study had, and a calculation based on an observed effect is not a substitute for a prespecified design rationale. The assumption of equal allocation between two arms also does not change the fact that the registry design is described as single-group and non-randomized with external data.

Why can over-dispersion matter?

For count outcomes, general models sometimes assume a particular relationship between the average count and its variability. Over-dispersion occurs when observed variability is greater than a model expects. If ignored, uncertainty estimates can be too small and inferential conclusions too confident. This is a general statistical consideration, not a method identified for CRYOFACTS. The primary endpoint is described as a participant count for a binary event, and the record does not report an over-dispersion assessment or any count model.

For this study, the central methodological limits are the absent endpoint estimate and interval, the non-randomized external comparison, and the lack of a reported statistical analysis plan or analysis records. General statistical principles can explain what estimates and intervals would mean, but they cannot fill in values or methods that are not reported in the registry record.

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("Focal Cryoablation Group", "External Data Supporting the Study")
n      <- c(75, 705)
events <- c(0, 0)
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  Focal Cryoablation Group  75  0  0.0  0.0  4.8  0.0  4.9  0.0  4.7
ARM  External Data Supporting the Study  705  0  0.0  0.0  0.5  0.0  0.5  0.0  0.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: the primary endpoint of persistent device- or procedure-related atrioventricular block through hospital discharge, and the secondary endpoint of atrioventricular block requiring insertion of a permanent pacemaker during defined follow-up. It lists no analysis records. The result for either endpoint, including any estimate, confidence interval, or hypothesis test, is not reported in the registry record.

When a study evaluates more than one outcome or performs multiple statistical tests, multiplicity can increase the chance of at least one apparently unusual result arising by chance. In general, a statistical analysis plan may specify which outcome is primary, which tests are confirmatory or exploratory, and whether any adjustment is used. The registry identifies a primary and a secondary outcome, but does not report whether multiplicity adjustments were planned or performed. The analysis hierarchy beyond the outcome labels is not reported in the registry record.

The record does not describe missing-data handling, the number of participants with available primary outcome data, exclusions from analysis, or analysis-population definitions. It also does not state how loss to follow-up or incomplete outcome assessment was handled. These details matter because the participants included in an outcome analysis may differ from those enrolled, and the handling of missing observations can affect estimates. Their absence does not establish that data were missing; it means the registry record does not provide the information needed to assess this issue.

Interim analyses and stopping rules are not reported in the registry record. Nor is a prespecified statistical analysis plan reported. These gaps limit assessment of whether the reported outcomes, if available elsewhere, were analyzed as planned and how uncertainty or multiplicity was addressed.

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 0% reporting threshold.

The registry lists serious adverse event figures for the focal cryoablation group and the external-data group. For the focal cryoablation group, 75 participants are listed at risk and 0 are listed as affected by a serious event; 0 are listed as affected by other events. For the external-data group, the corresponding at-risk count is 705, with 0 serious-event affected and 0 other-event affected. These are the figures recorded for the groups and categories identified in the registry.

At-risk counts and affected counts answer different questions: the former describe the group counted for safety reporting, while the latter describe recorded participants with the specified category of event. The groups have different sources and are not randomized, concurrent comparison groups. The external data were drawn from published reports, and the record does not describe whether their safety collection and follow-up were directly comparable with the focal group’s.

Zero affected entries should be interpreted as zero recorded in these registry fields, not as proof that the risk is absent. The record does not provide event-level details, the safety observation period, definitions beyond the serious-event categorization, or information about completeness of reporting. These safety counts also do not answer the primary endpoint question: the primary endpoint’s count and confidence interval are not reported in the registry record.

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

The CRYOFACTS registry record makes the study’s main safety question clear: it concerns persistent, device- or procedure-related atrioventricular block through hospital discharge after cryoablation for AVNRT. It also identifies a secondary outcome involving atrioventricular block that requires permanent pacemaker insertion during defined follow-up. These endpoint definitions help clarify which outcomes were of interest.

What the record does not establish is the observed primary endpoint result. It does not report how many participants met the primary definition, the corresponding 95% confidence interval, or the secondary outcome result. The listed safety figures are not a substitute for those endpoint results. They describe recorded serious and other adverse-event counts for the two safety groups, not the primary endpoint estimate.

The study is described as non-randomized, unmasked, and single-group, with a separate external-data arm. Consequently, any comparison with external reports would require caution. The available registry information does not establish that the study group and external reports were alike in their participants, follow-up, outcome definitions, or data collection. A contrast between them could not, by itself, show that the device or procedure caused a difference.

The discrepancy between listed enrollment of 105 and the primary endpoint timeframe stated as after 250 subjects have been enrolled also remains unexplained in the registry record. It is not possible to determine from these entries whether the endpoint was assessed at a different time or how the listed enrollment relates to the endpoint population. The completed status does not provide that missing information.

In general, a reported estimate with an interval can describe both the observed outcome and the statistical precision of that estimate. Here, neither is available for the primary endpoint. The appropriate reading is therefore limited: the registry describes a post-approval study and its intended outcomes, and it records safety counts, but it does not provide enough outcome information to quantify the primary event or assess its precision. No conclusion about treatment benefit or lack of benefit follows from the missing result.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks about a defined safety outcome after a marketed device procedure, while relying on a design that includes both a single-group study and external published data. Those features make careful separation of endpoint description, observed counts, and causal interpretation especially important. The record identifies a clinically specific event—persistent device- or procedure-related atrioventricular block through hospital discharge—but does not report its numerical result.

Its primary endpoint is a participant count accompanied by a planned 95% confidence interval. This highlights a key distinction in clinical statistics: a point estimate describes the observed data, while an interval conveys uncertainty around that estimate. The interval cannot be interpreted without the result, and neither can be inferred from enrollment or from separate adverse-event entries.

The external-data comparison also illustrates why study design matters. Published reports can offer context, but they are not equivalent to randomized, concurrent controls. Differences in participant selection, follow-up, outcome ascertainment, and reporting may complicate comparisons. The registry record does not describe these features sufficiently to determine how comparable the data sources are.

Finally, the endpoint timeframe states that assessment is after 250 subjects have been enrolled, while listed enrollment is 105. Because the record does not explain this discrepancy or provide the endpoint analysis, readers cannot determine how the intended timing relates to the completed study record. This is a useful reminder that a registered outcome definition and a completed status do not, on their own, supply analyzable results. Statistical interpretation depends on the reported estimate, its denominator, uncertainty, and the methods used to obtain it.

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.

Several trial-specific limitations are evident from the registry record. The primary endpoint is defined, but its participant count and 95% confidence interval are not reported. The secondary outcome result is also not reported, and its follow-up duration is unspecified. Without outcome values and the relevant analysis denominator, the event frequency and precision cannot be assessed.

The registry lists enrollment of 105, while the primary endpoint timeframe is stated as after 250 subjects have been enrolled. The record does not explain the difference, identify an alternate assessment point, or describe how many participants contributed to the primary analysis. This limits interpretation of the planned endpoint timing in relation to the completed study.

The non-randomized, single-group design and external-data arm limit the strength of any comparative interpretation. The registry does not provide details sufficient to assess comparability between the study group and the published reports, or to establish consistency in outcome definitions and follow-up. The lack of masking is recorded, but the endpoint assessment process and any measures to reduce assessment bias are not described.

Other unreported items include eligibility criteria, participant characteristics, the statistical analysis plan, sample-size justification, missing-data handling, analysis populations, interim analyses, and stopping rules. The record lists no analysis records. These omissions prevent a full assessment of how the intended outcomes were analyzed and how uncertainty was handled. They do not prove that particular procedures or analyses were absent; they are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CryoCath Freezor CryoAblation Catheter System (CRYOFACTS) — NCT00621621.
• Registry record last updated 2018-10-16; status last verified 2018-09.
• Results first posted 2015-04-23.
• 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

CRYOFACTS is a completed Phase 4 post-approval study of the Freezor Cardiac Cryoablation Catheter CryoConsole System for AVNRT. The registry lists a non-randomized, unmasked, single-group design, with an external-data arm drawn from peer-reviewed published reports. Enrollment is 105.

The primary outcome is the number of participants with device- or procedure-related atrioventricular block persistent through hospital discharge, with a 95% confidence interval specified. Its timeframe is stated as after 250 subjects have been enrolled. The primary result and confidence interval are not reported in the registry record. The secondary outcome concerns atrioventricular block requiring permanent pacemaker insertion during defined follow-up; its result and follow-up duration are also not reported.

Safety entries list 0 serious-event affected participants and 0 other-event affected participants in each group, with at-risk counts of 75 for the focal cryoablation group and 705 for the external-data group. These counts do not replace the missing primary endpoint result. No analysis records are listed.