Long-term Outcomes After Percutaneous Closure of PFO: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Outcomes After Percutaneous Closure of PFO (NCT05558774), a registered phase not stated study. The primary outcome is CVI.

2. Clinical Question

3. Trial Design

This is a clinical follow-up study of people after percutaneous closure of a patent foramen ovale. The registry identifies MC Medicor as the sponsor and lists the study status as COMPLETED. The recorded start date is 2022-07-11 and the primary completion date is 2024-10-01. Those registry dates describe the study record; they do not establish when every participant underwent closure or completed follow-up.

The brief summary describes an international medical centre in Slovenia and reports 363 successful percutaneous closures from October 2006 till October 2023. It says investigators plan clinical follow-up and contrast TTE to define the percentage of functional percutaneous closure. The registry enrollment is 364. The record does not explain the relation between enrollment and the 363 closures described in the summary, so the figures should not be treated as interchangeable denominators.

The primary outcome listed is CVI, described as cerebrovascular insult and measured as the number of participants with the outcome. The endpoint timeframe runs from the date of each individual closure until the last contrast TTE by protocol, with the phrase “in average 1.975 days from the procedure.” That wording is unusual in the context of the long period of closures described in the summary; its intended meaning is not reported in the registry record and should not be silently reinterpreted.

Five outcome measures are listed, with AF identified among the secondary outcomes. The detailed outcome definitions beyond the primary outcome are not reported in the registry record. No analysis is recorded, and there is no randomized allocation or like-for-like control comparison identified. Details of recruitment, follow-up completion, analysis populations and the statistical plan 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.

6. Primary Endpoint

The registry lists the primary outcome as CVI, measured over From the date of individual percutaneous closure until the date of the last contrast transthoracic echocardiogram by protocol, in average 1.975 days from the procedure..

The primary outcome is titled CVI, short for cerebrovascular insult in the registry description. Its unit is participants and its parameter is NUMBER. The registry’s stated meaning is participants with an event (counts). Thus, the intended summary is a count of participants recorded as having a cerebrovascular insult during the specified follow-up interval, rather than a time-to-event estimate or a continuous measure.

The timeframe begins on each participant’s date of percutaneous closure and ends at the last contrast TTE by protocol. The registry gives the phrase “in average 1.975 days from the procedure.” Because the wording does not clarify what the stated duration means, it cannot be used to infer a typical follow-up duration or to convert the outcome into a rate. Clarification is not reported in the registry record.

Counting participants with an event can describe how many people experienced the defined outcome in the observed study population. For interpretation, a count normally needs a clear denominator, consistent event definitions and information about follow-up; a count alone does not show the probability of an event over a fixed period or establish a causal effect. These are general statistical considerations. The posted results do not report a primary-outcome count, denominator, estimate or confidence interval, so the frequency and precision of CVI cannot be assessed from the registry record.

The brief summary emphasizes functional closure assessed with contrast TTE, but the listed primary outcome is CVI. The functional closure measure’s operational definition and results are not reported in the registry record. The stated primary outcome should therefore be kept distinct from the functional closure aim described in the summary.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

For a binary outcome, each participant is classified according to whether the defined event was recorded. A participant count reports how many people in the analyzed group met that definition. This is a general explanation of binary-outcome analysis. The registry identifies the primary outcome as a number of participants with an event, but does not post an analyzed count or denominator for CVI. Without both, readers cannot determine the observed proportion. The count also depends on how the event is defined, ascertained and attributed to the follow-up period; those operational details are not reported in the registry record.

Why does the denominator matter?

A count without its analysis denominator is difficult to interpret. The total enrolled is 364, while the brief summary describes 363 successful closures. The registry does not report which participants contributed to the primary-outcome analysis, whether anyone was excluded, or whether all participants had outcome ascertainment. It would be inappropriate to use enrollment or the closure count as an outcome denominator without confirmation. This is a general principle: the denominator should reflect the population actually evaluated for that outcome, not simply a nearby total from a different description.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater statistical precision than a wide interval, while neither alone establishes that an estimate is unbiased or clinically important. The posted results do not include a primary-outcome estimate or confidence interval, so precision cannot be described for CVI. The absence of an interval is not an interval centered at no effect and should not be read as evidence of equivalence.

Why can follow-up time affect interpretation?

The primary outcome timeframe is described as running from the date of each closure to the last contrast TTE by protocol. Participants may have different observation periods in follow-up studies; in general, this can affect the chance of having an event recorded. A participant count does not account for differing observation time in the way a time-to-event analysis can. The registry does not report individual follow-up durations, censoring information or a time-to-event analysis. The phrase “in average 1.975 days from the procedure” is recorded, but its meaning is not clarified. It should not be used to infer a duration or event rate.

What can planning calculations say?

Sample-size calculations are planning illustrations, not observations and not evidence that a study had a stated probability of detecting an effect. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. The assumptions also distinguish total events for time-to-event calculations from participants per arm for other calculations. However, no analysis is recorded, and no like-for-like randomized comparison is identified. The observed effect on which such illustrations would depend is not reported for the primary outcome. Any planning values must therefore be understood as hypothetical design illustrations, not as observed power or as a result of the study.

How should event counts be separated from comparisons?

An event count describes what was recorded in a group. A comparative effect requires a defined contrast between groups or another explicit comparison, together with an analysis appropriate to the design. The registry does not identify a comparator or allocation scheme. It specifically notes that the arms are not a like-for-like control comparison. Accordingly, a difference between any reported groups could not automatically be interpreted as a treatment effect, and no comparative estimate for CVI is posted. This is a general distinction between descriptive and causal statistical questions.

What is the role of over-dispersion?

General statistical note: over-dispersion occurs when count data vary more than a chosen model expects. If present, standard errors from a model that assumes less variability can be too small, making uncertainty appear understated. Model choice can therefore matter when analyzing counts, particularly when event rates differ across people or follow-up. The registry record does not report a count model, an assessment of over-dispersion or a fitted analysis for CVI. This concept explains a possible methodological concern in count analysis; it does not describe a method used in this study.

What analysis details are available?

The record lists five outcome measures and zero analyses. The statistical plan, model specifications, covariate adjustments, handling of repeated events and methods for missing data are not reported in the registry record. Without those details or posted outcome estimates, readers cannot reproduce an analysis or assess whether the analysis matched the stated endpoint. The record’s endpoint description and planning assumptions are not substitutes for a reported analysis.

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("Recurrent CVI")
n      <- c(355)
events <- c(1)
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  Recurrent CVI  355  1  0.3  0.0  1.6  0.0  1.6  0.1  1.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and identifies AF as a secondary outcome. No analyses are recorded. The registry record does not report a multiplicity strategy, such as whether any outcomes were designated as confirmatory or how interpretation would account for testing more than one outcome. In general, considering multiple outcomes can increase the chance of finding an apparently noteworthy result by chance if each is tested separately. That general concern cannot be quantified for this study from the posted results.

Missing-data methods are not reported in the registry record. There is no posted account of participants without a follow-up TTE, incomplete clinical follow-up, withdrawals, exclusions from analyses or how missing endpoint information was handled. The enrollment of 364 and the summary’s description of 363 successful closures do not establish how many people had complete data for each outcome. The analysis population for CVI is not reported.

It is also not reported whether the primary outcome was analyzed according to a prespecified plan, whether any outcomes were changed or added, or whether interim analyses took place. The registry record does not state the statistical analysis plan, and those details cannot be inferred from the endpoint label or the study’s completed status.

In general, missingness can affect both the denominator and the interpretation of an outcome, while multiplicity can affect how confidently findings across several outcomes are interpreted. These are methodological issues, not claims that either problem occurred in this study. With no analyses and no primary-outcome result posted, the effects of missing data or multiplicity on the findings cannot be evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tia (0.6%), cvi (0.3%).

The registry lists a group titled Detected Adverse Events. For serious events, 355 people are listed as at risk and 3 as affected. For other events, 355 are listed as at risk and 2 as affected. The deaths entry is 8. TIA and CVI appear among the top serious terms, reported as 0.6% and 0.3%, respectively. These are registry safety entries and should be read as such, not as estimates from a comparative safety analysis.

The meaning of “at risk” and “affected” is not further defined in the record. It does not clarify whether affected values count people, events or both, whether an individual can contribute to multiple categories, or how deaths overlap with serious and other events. The entries therefore should not be added together or treated as mutually exclusive categories. The 355 listed for each category also does not establish that the same analysis population or follow-up completeness applies to every outcome.

The percentages for TIA and CVI are recorded as 0.6% and 0.3%. The registry does not explain the denominator or calculation behind those percentages. They should not be converted into counts or compared with the affected counts without a stated method. The serious adverse-event entries do not replace the missing primary-outcome analysis, even though CVI is named in both contexts. The definitions, event ascertainment rules and relationship between safety reporting and the primary endpoint are not reported in the registry record.

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

The record describes a completed follow-up study after percutaneous PFO closure, with planned clinical assessment and contrast TTE. It names CVI as the primary outcome and records adverse-event information, including counts for serious and other events and deaths. These registry entries establish what the registry describes and what safety entries it contains; they do not provide an analyzed primary-outcome result.

Because no analysis is recorded, the posted information does not show how many participants experienced CVI in the primary analysis, what denominator was used, or how uncertain any estimate would be. It therefore cannot establish the frequency of the primary outcome in the analyzed population. Nor does the registry provide a comparison group from which to estimate a difference between closure and another approach. The lack of a reported estimate is not evidence of no events, and it is not evidence that groups were equivalent.

The registry’s purpose includes defining the percentage of functional closure, but the functional closure outcome and its results are not detailed in the posted record. The listed primary endpoint, CVI, should not be conflated with this stated functional-closure aim. The relation between the primary endpoint and the summary’s stated purpose is not explained.

The safety entries should also be interpreted narrowly. They identify reported counts and event terms, but do not establish comparative risk, causation or a complete account of all events. Definitions of the affected counts, the overlap between categories, and the basis for the listed percentages are not reported in the registry record.

In general, an observational follow-up description can be useful for documenting outcomes after a procedure, but causal conclusions require a design and analysis that address how outcomes would differ under an alternative. Here, allocation is not stated, no comparator is identified, and no primary analysis is posted. The record therefore supports a description of the study’s stated follow-up and recorded safety entries, but not a conclusion about treatment effect, outcome frequency or precision.

14. Why This Trial Matters Statistically

This record highlights an important statistical distinction between a study’s stated objective and its reported evidence. The brief summary describes follow-up intended to define functional closure after percutaneous PFO closure, while the registered primary endpoint is CVI. Both are clinically relevant areas of follow-up, but they answer different measurement questions. A functional imaging assessment and a count of participants with cerebrovascular insult cannot be treated as interchangeable outcomes.

The record also illustrates why enrollment totals are not necessarily analysis denominators. It lists enrollment of 364 and describes 363 successful closures, yet does not explain how those figures relate to the primary endpoint population. Statistical interpretation depends on knowing who was observed for each outcome and how missing information was handled. Without that information, even a reported count may be difficult to contextualize.

Another key issue is the difference between descriptive follow-up and comparative effectiveness. No comparator is identified and allocation is not stated. A follow-up record can document events among participants, but a causal comparison needs an appropriate contrast and an analysis that accounts for the design. The registry itself warns that the arms are not a like-for-like control comparison, so a group contrast should not be treated as a controlled treatment effect.

Finally, the absence of a posted primary analysis is itself consequential for interpretation. Endpoint definitions, planning assumptions and safety counts do not give an estimate of the primary outcome or its precision. This record therefore offers a useful example of how registration details can describe intended measurement while leaving the central statistical result unavailable. Readers need to distinguish those elements rather than infer a finding from the study’s completed status.

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 this specific record is that it lists no analyses. There is no reported CVI count, denominator, estimate, confidence interval or test. As a result, the primary outcome cannot be quantitatively evaluated from the registry record. The record’s completed status does not resolve this absence.

The endpoint timeframe includes the wording “in average 1.975 days from the procedure,” which is not clarified. The period described in the brief summary spans October 2006 till October 2023, but the registry does not explain how that period relates to the stated timeframe or individual follow-up. No follow-up distribution or censoring information is reported, limiting interpretation of event counts over time.

The registry enrollment is 364, while the brief summary reports 363 successful closures. The record does not explain this difference or specify which population contributed to each outcome. No participant characteristics, eligibility criteria, recruitment details or analysis population are reported. Consequently, the representativeness of the followed group and the completeness of outcome assessment cannot be assessed from the record.

The summary’s stated aim concerns functional closure assessed with contrast TTE, but the registry lists CVI as the primary outcome. Definitions and results for functional closure are not detailed. The secondary outcome list identifies AF, but the other outcome definitions and analyses are not reported in the registry record.

Finally, allocation is not stated and no comparator is identified. Details of event definitions, adverse-event ascertainment, missing-data handling, statistical methods and any adjustment strategy are not reported. These limitations prevent assessment of comparative effects, causal interpretation and analysis robustness, independent of whether events occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Outcomes After Percutaneous Closure of PFO — NCT05558774.
• Registry record last updated 2026-10-29; status last verified 2026-10.
• Results first posted 2026-10-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes follow-up after percutaneous closure of PFO, with clinical follow-up and contrast TTE in the brief summary. MC Medicor is listed as sponsor; the status is COMPLETED. Enrollment is 364, while the summary describes 363 successful closures from October 2006 till October 2023.

The primary outcome is CVI, described as cerebrovascular insult and measured as the number of participants with an event. AF is identified as a secondary outcome, and five outcome measures are listed. The record reports zero analyses, so no analyzed primary-outcome result or estimate of its precision is available.

Safety entries list 3 affected for serious events and 2 affected for other events, with 355 at risk for each; deaths are listed as 8. TIA and CVI are named among the top serious terms at 0.6% and 0.3%. Allocation and a comparator are not identified, and the relationship between the enrollment and closure totals is not explained.