iCLAS™ for Persistent Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for iCLAS™ for Persistent Atrial Fibrillation (NCT04061603), a na na study. The primary outcome is Analysis of the Proportion of Subjects Who Are Free From Device/Procedure Related Major Adverse Events (MAEs) That Occur Following the Cryoablation Procedure.

2. Clinical Question

That endpoint is a safety question rather than a direct measure of rhythm control or symptom improvement. The registry also lists acute procedural ablation success as a secondary outcome, but it does not provide a result for that outcome in the record described. The study began on 2019-12-09, had primary completion on 2023-08-30, and is recorded as completed. Its stated purpose was to evaluate the device and generate data to support a pre-market application. Because the study has one group and no control comparison, its registry information describes events observed among participants rather than the difference between iCLAS and another approach. The central interpretive issue is therefore whether the posted record contains the endpoint result needed to answer its own primary safety question: it does not. The available adverse-event counts provide some safety context, but they are not a reported estimate of the primary endpoint.

3. Trial Design

NCT04061603 is a completed clinical study of the Adagio AF Cryoablation System (iCLAS™) in people with persistent atrial fibrillation. The registry lists enrollment of 215 and describes an intervention group, iCLAS Ablation. The arm description says that the system was used for ablation of the left and right atrium. The study summary frames its purpose as evaluating safety and efficacy in symptomatic persistent atrial fibrillation and states that the data would support a pre-market application.

The registry identifies the study model as single group, masking as none, allocation as NA, and phase as NA. It therefore does not describe a randomized, blinded, parallel-group comparison. A comparator arm is not reported in the registry record. With no concurrent control group identified, observed counts cannot by themselves separate events associated with the device or procedure from events that might also occur in this population for other reasons. Nor can the record establish a comparative treatment effect.

The study started on 2019-12-09 and reached primary completion on 2023-08-30; its status is completed. The primary endpoint timeframe is 12-months. The endpoint population is defined separately from the total enrollment: it includes any enrolled subject, including roll-in subjects, for whom the venous access portion of the ablation procedure was initiated, regardless of whether ablation with the investigational device followed. The registry does not explain the difference between the enrollment figure and the adverse-event group’s at-risk count, so those figures should not be treated as interchangeable.

The record lists three outcome measures and zero analyses. It names acute procedural ablation success among the secondary outcomes, but does not provide an outcome result or an analysis description for that measure. Details of the protocol, the rationale for the enrollment target, and the planned statistical methods are not reported in the registry record. These omissions limit what can be concluded about how the study was designed to quantify uncertainty or handle outcomes beyond the endpoint definition itself.

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: 189 patients were treated with the investigational device

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population: Any enrolled subject (including roll-in subjects) who has the venous access portion of the ablation procedure initiated, regardless of whether the subject receives an ablation with the investigational device

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 Analysis of the Proportion of Subjects Who Are Free From Device/Procedure Related Major Adverse Events (MAEs) That Occur Following the Cryoablation Procedure, measured over 12-months.

The primary endpoint is the proportion of subjects free from device- or procedure-related major adverse events following the cryoablation procedure, with a 12-month timeframe. The registry defines the Safety Population as enrolled subjects, including roll-in subjects, whose venous access procedure was initiated, whether or not the investigational device was used to complete an ablation. This definition makes the population a procedural safety group rather than simply all enrolled subjects or only those who received a completed device ablation.

The listed major adverse events include death, myocardial infarction, cardiac perforation or pericardial tamponade, cerebral infarct or systemic embolism, major bleeding requiring transfusion, valve damage, pulmonary vein stenosis, permanent phrenic nerve injury, specified access-site complications, atrio-esophageal fistula, pericarditis, heart block requiring a permanent pacemaker, vagal nerve injury with gastrointestinal dysmotility, and other serious adverse device effects judged probably or definitely related by an independent Clinical Events Committee. The registry also specifies severe pulmonary vein stenosis as at least 70%.

A composite safety endpoint can collect clinically important events into one summary measure, but its interpretation depends on the event definition, population, follow-up, and adjudication rules. Different event types may vary in frequency and consequence, so a composite proportion does not convey each component’s individual course. The endpoint is useful for describing the proportion meeting a prespecified safety criterion, but the registry record does not report that proportion or its component results. The separate adverse-event counts should not be substituted for the missing primary endpoint result, because the record does not establish that those counts use the same event definition, attribution rule, or follow-up window.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical-trial results are easiest to interpret when the endpoint definition, population, follow-up period, and analysis are considered together. The iCLAS registry record defines a binary primary endpoint: whether a subject was free from the specified device- or procedure-related major adverse events over the stated 12-month timeframe. The outcome is framed as a proportion of participants, but the record does not provide the number meeting the criterion or the number included in its endpoint analysis. Without those pieces, the primary proportion cannot be interpreted quantitatively.

What does a proportion describe?

A proportion summarizes how many members of a defined group meet a condition, relative to the number assessed. For a safety endpoint, the condition might be freedom from the endpoint events or occurrence of at least one such event, depending on how the outcome is reported. The registry title asks about the proportion free from major adverse events. The posted record does not report that proportion. The adverse-event group count is not automatically its complement: the primary endpoint has a specific relationship, attribution requirement, population definition, and follow-up period, and the posted adverse-event counts are not shown to be a matching endpoint analysis.

Why does the population definition matter?

The stated Safety Population includes any enrolled subject whose venous access portion of the procedure was initiated, including roll-in subjects, whether or not the subject received investigational-device ablation. This rule determines who should contribute to the safety assessment. A different population, such as all enrolled subjects or only those who completed an ablation, could yield a different denominator and answer a different question. The adverse-event record gives an at-risk count of 189, while total enrollment is 215. The record does not explain the relationship between these counts, so they should remain distinct rather than being reconciled by assumption.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and a particular sampling process. It helps distinguish a precisely estimated quantity from one with substantial uncertainty. For a proportion, the interval reflects both the observed proportion and the amount of information available. No confidence interval for the primary endpoint is reported in the registry record. There is therefore no reported precision measure with which to judge the primary result, even if the endpoint definition is clear.

What does a single-group design allow?

A single-group design can describe outcomes observed among participants who received the study intervention or entered the defined safety population. It does not, by itself, estimate a randomized difference from a control group. Background risks, participant characteristics, procedural context, and other factors may influence observed events. Without a comparison group, those influences cannot be separated from intervention-associated outcomes through a between-group contrast. The registry lists allocation as NA and the model as single group; a comparator is not reported in the registry record.

How should event categories be read?

A composite endpoint combines multiple specified event types into one outcome. That can make a broad safety question easier to summarize, but it also means the total depends on which events qualify and how they are attributed. The primary definition includes multiple event types and says that other serious adverse device effects must be adjudicated by an independent Clinical Events Committee as probably or definitely related to the Adagio System. The record does not supply the primary endpoint’s component counts or its final composite result. Separately posted serious and other adverse-event counts should not be assumed to follow every rule in the primary endpoint definition.

Adverse-event terms and event counts can also differ in unit. A count may refer to events, participants with an event, or categories of events; recurrent events can make those quantities distinct. The registry describes the posted adverse figures as affected counts, but does not provide event-level detail to establish overlap among categories. The serious-event count, other-event count, and death count should therefore be read separately, not summed into a new total. The percentages attached to serious-event terms are reported values; they should not be treated as a complete partition of all serious events unless the registry specifies that interpretation.

What does the analysis record tell us?

The registry reports zero analyses. This means the record does not include a posted analysis result for the listed outcomes in the information summarized. It does not establish which statistical model, confidence-interval method, handling of missing observations, or interim-monitoring approach was used; those details are not reported in the registry record. General statistical concepts cannot fill in a trial’s unreported methods. No sponsor analysis result is available in this record to compare with a recalculation.

The record also does not report a sample-size justification or a planned statistical analysis. Enrollment of 215 is a study descriptor, not evidence by itself that the study had a particular level of statistical power. Power is a planning concept tied to assumptions about an effect, variability or event probability, significance level, and analysis. It is not an observed property that can be inferred from enrollment alone. In the absence of the protocol assumptions and a primary endpoint result, no conclusion about the study’s planned or achieved precision should be drawn from the count of enrolled participants.

In general, missing outcome data can affect an estimate if participants with unavailable measurements differ from those with observed measurements. A complete analysis would clarify who was assessed, how missing follow-up was handled, and whether exclusions occurred. Those details are not reported in the registry record for the primary endpoint. The endpoint’s Safety Population definition offers a population rule, but it does not disclose the actual endpoint denominator or the disposition of every participant. Thus the central statistical limitation is not a complex calculation: the registry presents the endpoint question without the result and analysis needed to quantify its answer.

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("Safety Cohort")
n      <- c(189)
events <- c(3)
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  Safety Cohort  189  3  1.6  0.3  4.6  0.5  4.6  0.6  4.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary safety endpoint and acute procedural ablation success as a secondary outcome, but reports zero analyses. It does not describe a statistical analysis plan, the order in which outcomes would be tested, or any adjustment for multiple comparisons. Whether multiplicity was considered is not reported in the registry record. Without that information and without posted analysis results, there is no basis for interpreting a collection of p-values or deciding whether a testing strategy controlled the chance of false-positive findings.

Missing outcome data are also not described. The record defines the Safety Population as subjects with venous access initiated, including roll-in subjects and regardless of whether they received an investigational-device ablation. However, it does not report how many members of that population had an observed 12-month endpoint assessment, whether any were excluded from the analysis, or how unavailable follow-up was handled. The at-risk count in the adverse-event record does not resolve those questions because the record does not state that it is the endpoint analysis denominator.

The registry does not report a statistical plan for interim analyses, stopping rules, or sample-size justification. These design and analysis details should not be inferred from the completed status or enrollment figure. Nor does the record identify an analysis population beyond the Safety Population definition given for the endpoint. In general, the choice of analysis population and the treatment of missing data can affect the meaning of a result; here, no primary endpoint estimate is posted to evaluate under any such 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vascular access site complications (1.6%), phrenic nerve injury (1.1%), esophageal injury (1.1%), pulmonary hypertension (0.5%), cerebral infarct or systemic embolism (0.5%).

The iCLAS Ablation adverse-event record lists 189 at risk, 10 serious adverse events, 14 other adverse events, and 3 deaths. The serious-event terms and their posted percentages are vascular access site complications at 1.6%, phrenic nerve injury at 1.1%, esophageal injury at 1.1%, pulmonary hypertension at 0.5%, cerebral infarct or systemic embolism at 0.5%, and vascular access site bleeding at 0.5%. These are descriptive registry entries, not a comparative safety analysis.

The categories should be kept separate. The record does not establish whether serious events, other events, and deaths overlap, or whether the counts refer to unique participants across all categories. It would therefore be inappropriate to add the counts into a total or calculate a new proportion from them. The adverse-event entries also should not be treated as equivalent to the primary endpoint: that endpoint specifically concerns freedom from device- or procedure-related major adverse events over 12 months, with defined criteria and adjudication language. The record does not identify which posted adverse-event entries meet that exact definition.

These figures provide limited information about recorded events in the study group. They do not describe comparative risk, establish causation, or replace the unreported primary endpoint result. Event timing, recurrence, severity detail, and category overlap are not reported in the registry record.

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

The record establishes that a completed, single-group study evaluated the Adagio AF Cryoablation System (iCLAS™) in persistent atrial fibrillation and specified a 12-month primary safety endpoint. It also lists adverse-event counts and serious-event terms for the iCLAS Ablation group. Those details describe the study’s question and some of its posted safety information. They do not provide the primary endpoint result.

In particular, the registry record does not report the proportion of the defined Safety Population who were free from device- or procedure-related major adverse events. No confidence interval or inferential analysis for that outcome is reported. Consequently, the record does not show how precisely the primary safety question was answered, or whether the endpoint’s criterion was met. A completed status does not supply a missing result.

The adverse-event counts cannot be used to infer the missing primary outcome. The primary endpoint uses a particular event set, attribution rule, population, and follow-up period. The posted serious-event, other-event, and death counts are not documented as a direct accounting of that endpoint. They also do not establish a comparison with another treatment, because the registry describes a single-group study and does not report a comparator.

More generally, an observed safety count is descriptive. In a one-group study, it cannot alone identify how many events would have occurred under another approach or separate intervention-related events from other causes. The listed serious-event terms may be useful context, but the record does not supply sufficient event-level details to interpret them as a complete account of the composite endpoint. The most appropriate conclusion is limited: the registry defines the safety question and posts some adverse-event information, while leaving the primary endpoint outcome and its uncertainty unreported. No conclusion about comparative effects or efficacy can be drawn from these data alone.

14. Why This Trial Matters Statistically

This study illustrates why a registry’s endpoint definition and its endpoint result must be read separately. The primary safety question is specific: freedom from device- or procedure-related major adverse events in a defined Safety Population over 12 months. That level of detail allows a reader to understand what the study intended to assess. Yet without a reported numerator, denominator, or proportion, the endpoint cannot be evaluated quantitatively. A precise endpoint definition is important, but it is not a substitute for the result.

The design also matters. The registry identifies a single-group model and no randomized comparison. That structure can support description of outcomes in the study group, but it does not provide a randomized estimate of how outcomes differ from a control group. For clinical researchers and biostatisticians, this distinction separates a descriptive safety account from a comparative treatment-effect analysis. It prevents the posted event counts from being read as evidence about what would have happened under a different intervention.

The case also shows why counts with different labels should not be combined casually. The adverse-event record separately lists serious events, other events, deaths, and named serious-event terms. The primary endpoint has its own eligibility and attribution criteria. Without a documented mapping among these categories, an analyst cannot treat the adverse-event entries as the endpoint result or construct a new total from them.

Finally, the record’s zero analyses and absence of a reported primary result leave uncertainty about the actual statistical approach, missing-data handling, and precision. Those omissions are consequential for interpretation, not merely technical details. A study may be completed and have a clearly stated objective while the registry record still lacks the information needed to answer that objective. This distinction is useful when assessing what registry evidence can support and when identifying which conclusions must remain open.

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 this study from the registry record is that the primary endpoint result is not reported. The endpoint definition and its 12-month timeframe are available, but the record does not give the number or proportion of the Safety Population who were free from the specified major adverse events. It also does not report a confidence interval or an analysis result. The primary safety question therefore remains quantitatively unanswered in the registry information described.

The single-group design limits comparative interpretation. The record does not identify a control arm or randomized contrast, so the posted adverse-event counts cannot estimate a difference against another intervention. The record does not provide an analysis that adjusts for other factors, and such an analysis should not be assumed.

The enrollment figure of 215 and the adverse-event at-risk count of 189 are both reported, but the registry record does not explain their relationship. The primary endpoint definition gives the Safety Population rule, but the record does not state the actual denominator used for an endpoint analysis or describe missing 12-month assessments. It also does not report how any incomplete follow-up was handled.

Additional limitations include the absence of a reported statistical analysis plan, sample-size justification, interim-analysis information, and multiplicity strategy. The record lists three outcome measures and zero analyses, but does not give the results for acute procedural ablation success or other outcome measures. The adverse-event entries do not establish whether categories overlap, how events were counted over time, or which events satisfy the primary endpoint’s device- or procedure-related criteria. These gaps restrict conclusions to the study description and the adverse-event information actually posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: iCLAS™ for Persistent Atrial Fibrillation — NCT04061603.
• Registry record last updated 2026-08-06; status last verified 2026-07.
• Results first posted 2026-08-06.
• 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.

19. Record Summary

NCT04061603 is a completed, single-group study of the Adagio AF Cryoablation System (iCLAS™) for persistent atrial fibrillation. The registry lists enrollment of 215, no masking, and an intervention group described as receiving left- and right-atrial ablation. The study began on 2019-12-09 and reached primary completion on 2023-08-30.

The primary endpoint asks what proportion of a defined Safety Population were free from device- or procedure-related major adverse events at 12 months. The registry record does not report that endpoint result or an analysis for it. It lists an adverse-event at-risk count of 189, 10 serious adverse events, 14 other adverse events, and 3 deaths, along with several serious-event terms and percentages. These data do not replace the missing primary endpoint estimate or provide a randomized comparison. The record lists three outcome measures and zero analyses; further statistical planning, missing-data, and analysis details are not reported in the registry record.