HEAL-LAA Clinical Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HEAL-LAA Clinical Trial (NCT05809596), a na na study. The primary outcome is Primary Efficacy Endpoint: The Rate of Device Leak >5 mm at 45-day Post-Implant TEE for the Primary Analysis Subjects.

2. Clinical Question

3. Trial Design

HEAL-LAA is a completed, single-group, post-market real-world outcomes study of the WATCHMAN FLX Pro left atrial appendage closure device. The registry lists enrollment as 949, with a start date of 2023-10-03 and primary completion date of 2024-07-15. The study status is completed. Its stated objective is to collect real-world data in patients with non-valvular atrial fibrillation.

The listed intervention is WATCHMAN FLX Pro device implantation, and the arm description identifies a Device Group. The design is single group, allocation is NA and masking is none. There is no randomized comparator described, so the study does not provide a treatment-versus-control contrast. The phase is listed as NA. Further details about recruitment, eligibility, the clinical setting, procedural practice and follow-up beyond the specified endpoint time are not reported in the registry record.

The primary efficacy endpoint is a count of participants with device leak greater than 5 mm at 45-day TEE imaging, among implanted primary analysis subjects with that imaging. The description says the assessment is made by a core lab. The record lists two outcome measures but no analysis entries. The primary endpoint result, including its numerator and denominator, is not reported in the registry record. The number enrolled should not be treated as the size of the endpoint population: the registry defines the primary analysis population by implantation and availability of 45-day TEE imaging, and does not report its size.

Because there is no randomized control group, outcomes describe the observed experience in the study population rather than a causal comparison with an alternative. That distinction matters when interpreting both effectiveness-related outcomes and adverse events. Details of any protocol-defined analysis, sample-size justification or interim monitoring 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:

Analysis population for the primary outcome, as defined in the registry: Implanted primary analysis subjects with 45-day TEE imaging.

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 Primary Efficacy Endpoint: The Rate of Device Leak >5 mm at 45-day Post-Implant TEE for the Primary Analysis Subjects, measured over 45 days.

The primary endpoint is the count of participants with a peri-device gap greater than 5 mm at 45-day post-implant TEE imaging. It applies to implanted primary analysis subjects who had 45-day TEE imaging, and the description says the core lab assessed the seal. The endpoint title describes a rate, while the listed parameter is a count of participants. The event criterion, assessment method, population and time point are stated; the result is not reported in the registry record.

In general, an imaging endpoint can describe a device-related finding at a defined assessment time. A specified gap threshold makes the event definition more explicit, while a core-lab assessment can support consistent interpretation of images. These features do not, on their own, establish the clinical consequences of a finding or show how often it occurred. Those interpretations require the observed count, the endpoint denominator and relevant follow-up information.

The registry record does not provide the number of participants meeting the leak criterion, the number assessed, or an uncertainty interval for the endpoint. The overall enrollment of 949 is not a substitute for the endpoint denominator, because the endpoint population is defined by implantation and 45-day imaging. Without the result and denominator, the endpoint cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary endpoint in terms of participants with an event, reported as a count. The primary event is a peri-device gap greater than 5 mm on 45-day TEE imaging. The defined population is implanted primary analysis subjects who had that imaging, and the assessment is described as being made by a core lab. The record does not report the observed count or the number assessed, so no endpoint estimate or precision measure can be interpreted.

What does a participant count represent?

In general, a participant count reports how many people meet a stated event definition. A proportion or rate additionally requires a denominator, such as the number of participants assessed for that outcome. Counts and proportions answer related but different questions: a count conveys the number observed, while a proportion places that count in relation to the population assessed. Neither can be recovered from an enrollment total when the endpoint population is separately defined and its size is not reported.

Here, the endpoint title uses the word “rate,” but the listed parameter is a count of participants. The registry record gives the event threshold and assessment time but not a result, denominator or calculated rate. That prevents a reader from checking the numerical relationship between the endpoint title and a reported analysis.

What would an uncertainty interval add?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, and it does not address all sources of bias or measurement error. For a participant proportion, interval width is influenced by the amount of information in the analyzed population and by the observed event frequency. The registry record does not report an endpoint estimate or confidence interval, so the precision of the primary result cannot be evaluated.

A p-value, in general, quantifies how compatible data are with a specified null model under an analysis plan. It does not measure clinical importance, prove causation or replace an effect estimate and its uncertainty. No primary endpoint p-value or corresponding test is reported in the registry record. Moreover, with no randomized comparator group described, a test of a treatment contrast is not available from the design details in the record.

Why does the population definition matter?

The primary endpoint is restricted to implanted primary analysis subjects who had 45-day TEE imaging. This is not automatically the same group as everyone enrolled. In general, when an outcome is assessed only in a subset, the result describes that subset unless the analysis accounts for differences between assessed and unassessed participants. The registry record does not report the subset size, the number without imaging, reasons for unavailable imaging, or methods for handling missing outcomes. It is therefore not possible to assess how complete the endpoint ascertainment was.

The core-lab assessment is part of the endpoint definition. In general, a central assessment process can help standardize interpretation, but a registry description alone does not establish how disagreements, unreadable images or missing assessments were handled. Those procedural details are not reported in the registry record.

How should planning illustrations be read?

In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, significance level, allocation and analysis method. The registry's stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect expressed as a fraction of the observed effect. Such assumptions do not describe the single-group design as randomized, and any calculated sample sizes are illustrations rather than observed power. They are not evidence that the trial was adequately powered or that an outcome was statistically significant.

The stated assumptions also distinguish time-to-event calculations, which use total events under the Schoenfeld approach, from other calculations, which give participants per arm. The primary endpoint is specified as a participant count at 45 days, not as a time-to-event endpoint. Numerical planning results and a trial-specific sample-size justification are not reported in the registry record. In general, over-dispersion matters when count data vary more than a chosen statistical model expects, because standard errors and intervals can then be too small if that extra variation is ignored. The record does not describe a count model or an over-dispersion assessment for the primary endpoint.

Finally, the record lists 0 analysis entries. Statistical methods beyond the endpoint description and the planning assumptions are not reported in the registry record. No adjustment method, covariate model, missing-data procedure or prespecified sensitivity analysis can be inferred from the available design description.

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("Primary Analysis Subset")
n      <- c(404)
events <- c(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  Primary Analysis Subset  404  0  0.0  0.0  0.9  0.0  0.9  0.0  0.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 0 analysis entries. It does not report a multiplicity strategy, such as how statistical error would be controlled across multiple endpoints or analyses. In general, when several outcomes or tests are examined, the chance of at least one apparently unusual result can increase; a prespecified testing strategy helps clarify how such results should be interpreted. No such strategy is reported in the registry record, and no p-values are provided for the primary endpoint.

Missing data are also relevant because the primary efficacy population is defined as implanted primary analysis subjects with 45-day TEE imaging. The registry record does not report how many eligible participants lacked imaging, whether assessments were unreadable, why imaging might be unavailable, or how missing outcomes were handled. It does not describe imputation, complete-case analysis or sensitivity analyses. In general, incomplete outcome ascertainment can affect both the population represented by an estimate and its uncertainty; the extent of that issue cannot be evaluated without the missingness information.

The phrase “primary analysis subjects” identifies a population but does not provide a fuller analysis-population definition. The registry record does not report whether all implanted participants were included in safety analyses, how deviations from the intended assessment were treated, or how analysis populations were selected. A sample-size justification and any interim analysis plan are also not reported in the registry record. These omissions limit assessment of whether analysis choices were prespecified and how robust any reported result might be; no endpoint result is reported to assess in the first place.

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: atrial fibrillation (2.6%), gastrointestinal haemorrhage (2.4%), cardiac failure acute (2.2%), cardiac failure congestive (1.8%), acute respiratory failure (1.4%).

The registry lists a Primary Analysis Subset with 500 participants at risk for serious adverse events and 141 participants affected. It also lists 500 at risk for other adverse events and 70 affected, along with 16 deaths. These are descriptive safety figures for the listed group. They are not a comparison with an untreated group or another device group, because no randomized comparator is described.

The registry also lists serious adverse-event terms and percentages: atrial fibrillation, 2.6%; gastrointestinal haemorrhage, 2.4%; cardiac failure acute, 2.2%; cardiac failure congestive, 1.8%; acute respiratory failure, 1.4%; and acute kidney injury, 1.2%. The registry record does not report the denominators or follow-up window for these term-specific percentages, or whether participants could contribute to more than one term. They should therefore be read as reported descriptive percentages, not as comparative risks.

In general, an adverse event recorded after an intervention is not necessarily caused by that intervention. The record does not establish causality for the listed events. It also does not provide enough detail to determine how the safety subset relates to the primary efficacy population or to the full enrollment. These figures describe reported safety experience; they do not establish a causal effect or a comparison of safety between treatments.

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

The record establishes that HEAL-LAA was a completed, single-group post-market study of WATCHMAN FLX Pro implantation, with a stated objective of collecting real-world data in patients with non-valvular atrial fibrillation. It defines a primary efficacy endpoint based on device leak greater than 5 mm at 45-day TEE imaging in implanted primary analysis subjects with imaging. That definition conveys what the endpoint was intended to measure, but the observed primary result is not reported in the registry record.

Without the event count and endpoint denominator, the endpoint frequency cannot be described. Without an estimate and uncertainty interval, its statistical precision cannot be judged. The listed enrollment of 949 does not fill that gap because the primary analysis population is separately defined and its size is not reported. The record's lack of an analysis entry also means that no reported inferential result is available to interpret.

The study design does not include a randomized comparator. In general, a single-group study can document outcomes observed among its participants, but it cannot by itself estimate what would have happened to comparable participants under another treatment. Differences in patient characteristics, clinical practice and other influences cannot be separated from the intervention using a randomized contrast that is not part of the design.

The safety information gives counts for affected participants and a list of serious adverse-event terms with percentages. Those data can be read as descriptive reports for the listed subset. They do not show comparative safety, establish that an event was caused by the device, or indicate how the figures compare with another treatment. The registry record does not report a safety follow-up window or the term-specific denominators.

Accordingly, the registry record describes the study's question and design and includes selected safety figures, but does not provide the primary efficacy result. That absence should not be interpreted as zero events, evidence of no leak, or evidence for or against a treatment effect. The available information does not support a conclusion about comparative effectiveness or causality.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a clearly defined endpoint and a reported endpoint result. The registry specifies the imaging criterion, the assessment time and the primary analysis population. Those details are essential for understanding what would count as an event and to whom the result would apply. Yet the event count, denominator and uncertainty are not reported in the registry record, so the endpoint cannot be quantitatively interpreted.

The design also illustrates why study structure determines the kinds of conclusions statistical analysis can support. A single-group study can describe outcomes observed after implantation. It does not provide a randomized control comparison, and therefore does not separate an intervention-associated outcome from other explanations in the way a randomized contrast is designed to do. The registry lists allocation as NA and masking as none, so a comparative treatment estimate should not be inferred.

Population definitions matter as well. Enrollment is listed as 949, while the endpoint applies to implanted primary analysis subjects with 45-day TEE imaging. The size of that endpoint subset is not reported. This makes it impossible to determine from the registry record how much of the enrolled population contributes to the primary endpoint or how missing imaging might affect interpretation.

The safety data highlight a related point: event counts and term-specific percentages can describe reported experience, but without a comparator, denominators and follow-up details they do not establish comparative risks or causality. The record's 0 analysis entries further limit assessment of the statistical methods used. These features make careful separation of design, outcome definition and observed result particularly important when reading real-world device evidence.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It gives the event definition and assessment time but no count, denominator, rate or uncertainty interval. The overall enrollment of 949 cannot substitute for the endpoint population size, which is defined by implantation and 45-day TEE imaging and is not reported in the registry record.

The design is single group, with no randomized comparator described. This limits interpretation to reported experience in the study population and does not support a randomized estimate of the device's effect relative to another treatment. Masking is listed as none. The registry record does not report further details about endpoint adjudication beyond core-lab assessment, or how image quality, disagreements or unavailable assessments were handled.

Information about eligibility criteria, participant characteristics, clinical practice, follow-up completeness and reasons for missing imaging is not reported in the registry record. These details would help readers judge which patients the observations represent and whether participants with available imaging may differ from those without it. A trial-specific sample-size justification, analysis plan, interim analyses, multiplicity handling and missing-data methods are also not reported.

Safety interpretation is limited by the absence of a comparator and by missing context for the listed adverse-event counts and percentages. The registry record does not report the safety follow-up window, term-specific denominators or the relationship between the safety subset and the efficacy population. It also does not establish causality for the events. Together, these limitations mean the posted information is descriptive and incomplete for evaluating endpoint frequency, precision or comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HEAL-LAA Clinical Trial — NCT05809596.
• Registry record last updated 2025-11-04; status last verified 2025-10.
• Results first posted 2025-10-15.
• 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

HEAL-LAA (NCT05809596) is a completed, single-group post-market study of WATCHMAN FLX Pro left atrial appendage closure device implantation. The registry lists enrollment as 949, a start date of 2023-10-03 and a primary completion date of 2024-07-15. The stated objective is to collect real-world data in patients with non-valvular atrial fibrillation.

The primary efficacy endpoint is the count of participants with a peri-device gap greater than 5 mm at 45-day TEE imaging, among implanted primary analysis subjects with imaging; assessment is described as core-lab based. The endpoint result, analysis population size and uncertainty are not reported in the registry record. The record lists 2 outcome measures and 0 analysis entries.

Safety information lists 141 participants affected by serious adverse events and 70 affected by other adverse events among 500 at risk in each category, plus 16 deaths. Serious adverse-event terms and percentages are reported, but the safety data are not a randomized comparison and do not establish causality.