Closure of Muscular Ventricular Septal Defects (VSDs) With the AMPLATZER Muscular VSD (MuVSD) Occluder - Post Approval Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Closure of Muscular Ventricular Septal Defects (VSDs) With the AMPLATZER Muscular VSD (MuVSD) Occluder - Post Approval Study (NCT00647387), a na na study. The primary outcome is Primary Effectiveness End Point: Technical Success.

2. Clinical Question

3. Trial Design

This is a completed, single-group post-approval study of the AMPLATZER Muscular VSD Occluder. The registry records enrollment of 92 and a study start of 2008-03; primary completion is recorded as 2024-02-23. The study status is COMPLETED. Its stated purpose was to further evaluate safety and effectiveness in subjects implanted with the device.

There is no concurrent control arm: the model is single-group and allocation is recorded as NA. Masking is recorded as NONE. The phase entry is NA. These entries do not establish a comparative treatment effect, and no randomized comparison can be inferred from the study design. The intervention is device implantation, described as implantation with the Muscular VSD Occluder.

The primary endpoint is technical success during the procedure. Its analysis population is specified as prospectively enrolled subjects only, N=80, with an attempted device placement. An attempt is defined as the delivery system entering the subject's body in an effort to place a device. The record states that retrospectively enrolled subjects were selected based on established technical success; the remaining explanation is incomplete in the registry record. This distinction matters because the primary endpoint population is not simply all enrolled participants.

The registry records four outcome measures and no listed analyses. It does not report a sample-size justification, statistical analysis plan, or rationale for the enrollment target in the record. Safety information includes serious adverse event counts, other adverse event counts, deaths, and listed serious event terms. These descriptive safety data do not create a control group or establish whether an event was caused by the device.

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: The analysis population included all prospectively enrolled subjects only (N=80) who have an attempted device placement (defined as the delivery system enters the subject's body in an attempt to place a device), as retrospectively enrolled subjects were selected based on established Technical Success.

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: Analysis included prospectively (n=80) and retrospectively (n=12) enrolled subjects.

6. Primary Endpoint

The registry lists the primary outcome as Primary Effectiveness End Point: Technical Success, measured over During the procedure.

The primary effectiveness endpoint is technical success, measured as a count of participants. It concerns whether the device was successfully deployed in participants with a ventricular septal defect. The assessment timeframe is during the procedure, so this endpoint captures immediate procedural deployment rather than longer-term clinical status or durability.

A technical endpoint is useful in a device study because successful deployment is a direct procedural milestone: it indicates that placement was achieved according to the endpoint definition. It is not, by itself, a complete measure of safety, subsequent health outcomes, or sustained effectiveness. Those questions require other outcomes and suitable follow-up information.

The specified analysis population includes prospectively enrolled participants with an attempted placement, N=80. An attempt is defined as the delivery system entering the subject's body in an attempt to place a device. The record says retrospective enrollees were selected based on established technical success. Restricting the primary population to prospective enrollees therefore distinguishes the planned effectiveness assessment from retrospective cases selected using knowledge of the endpoint. The full rationale is not reported in the registry record.

The endpoint definition and population are described, but the number of participants with technical success is not reported in the registry record. Without that result, the observed success proportion, its uncertainty, and any comparison with a target cannot be evaluated. No target or benchmark is reported either.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Technical success is a binary outcome at the participant level: a participant either meets the stated deployment definition or does not. The registry presents the outcome measure as a count of participants. For a binary endpoint, a complete report commonly gives the number meeting the definition, the number assessed, and an uncertainty interval for the underlying event probability. The technical-success count and uncertainty interval are not reported in the registry record, so no such estimate can be interpreted.

What does a single-group design estimate?

A single-group study describes outcomes observed in the group that received the intervention. It does not directly estimate a difference between treatments because there is no concurrent comparison group. A single-group event frequency may still be clinically and procedurally informative, but its meaning depends on the population, endpoint definition, follow-up, and completeness of outcome ascertainment. It cannot by itself distinguish the effect of the device from other influences.

In a randomized comparison, random allocation helps balance measured and unmeasured factors on average between groups. This study has no randomized allocation and no control group, so that protection against confounding is absent. An external comparison could be considered only with a clearly defined and appropriate reference population and compatible outcome measurement. Such a comparison is not reported in the registry record.

Why does the analysis population matter?

The primary population is described as prospectively enrolled participants with attempted placement, N=80. The attempt definition is procedural: the delivery system enters the participant's body in an effort to place a device. This defines who is eligible for the primary technical-success assessment. Enrollment of 92 is a separate registry figure and should not be treated as the endpoint denominator: the record gives the narrower primary population explicitly.

The record notes that retrospective enrollees were selected based on established technical success. Including cases selected using knowledge of their outcome could make a success count difficult to interpret as an unbiased description of all attempted placements. The prospective restriction addresses that distinction in the stated population, but the registry record does not provide a full protocol explanation or enough detail to assess all possible selection mechanisms.

What does precision mean?

An estimate from a sample is subject to uncertainty. A confidence interval expresses a range of values that are compatible with the observed data under the statistical model and its assumptions. A narrower interval indicates greater statistical precision, while a wider interval indicates more uncertainty. An interval does not resolve bias, confounding, incomplete follow-up, or limitations in how the endpoint was measured. No interval for the primary endpoint is reported in the registry record.

For a binary endpoint, precision depends in part on the number of participants assessed and the number with the event. Because the primary success count is missing, neither its estimate nor its precision can be reconstructed from the information in the record. Reconstructing a result from the enrollment figure alone would be inappropriate.

How should planning calculations be read?

Any sample-size calculations associated with this study are planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumptions describe hypothetical future planning, not the design of this single-group study. The calculations are not observed power and do not show that the study was adequately powered. The registry record does not report the sample-size justification used for the study itself.

In general, a planning calculation asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen probability. Results depend on the assumed effect, allocation, endpoint, and statistical method. If the assumed effect is smaller, planning generally requires more information to detect it. A planning illustration cannot substitute for a trial's analysis plan or supply a missing primary result.

Why do event definitions and distributions matter?

Safety outcomes are counts of participants with events in this record. Serious adverse events, other adverse events, and deaths are separate reported categories. The registry also lists selected serious event terms with percentages. A participant can potentially experience more than one event, so event-term percentages should not be summed or interpreted as mutually exclusive categories unless the record establishes that structure. The record does not specify the event-term counting method in enough detail to make that assumption.

In general, event counts can vary more than a simple probability model expects when risks differ across participants or when observations are clustered. Over-dispersion is the term for variability greater than a model assumes; ignoring it can make uncertainty appear too small. The registry does not report a model for these safety summaries, and no model-based inference should be attributed to them.

The record lists no analyses. It does not report a statistical analysis plan, confidence intervals, hypothesis tests, adjustments, or interim analyses. Their presence or absence in the underlying study cannot be inferred beyond what is recorded. Accordingly, interpretation should remain descriptive and tied to the stated endpoint definitions and populations.

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("Muscular VSD Occluder")
n      <- c(80)
events <- c(75)
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  Muscular VSD Occluder  80  75  93.8  86.0  97.9  86.2  97.3  86.2  97.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures but no analyses. It does not report whether a multiplicity strategy was specified, such as prioritizing endpoints, adjusting significance thresholds, or treating secondary outcomes as exploratory. When several outcomes are assessed, the chance of at least one apparently unusual result can increase if each is tested separately. A prespecified strategy helps clarify which findings are confirmatory and how uncertainty should be interpreted. No such strategy is reported in the registry record.

Missing-data handling is also not reported in the registry record. The record does not state how unavailable endpoint assessments, withdrawals, or incomplete follow-up were handled, or whether all participants in the primary population had an evaluable technical-success outcome. It is therefore not possible to assess whether the reported enrollment and analysis populations differ because of missing outcomes.

The primary effectiveness population is explicitly limited to prospectively enrolled participants with an attempted device placement, N=80; retrospective enrollees were selected based on established technical success. This is a population definition, but the record does not provide a complete account of the analysis process or the outcome status of participants outside that population. No imputation method, sensitivity analysis, or missingness assumption is reported.

The distinction matters because results can be sensitive to who is included and how unavailable outcomes are treated. A transparent report would describe the number assessed, reasons for missing outcomes, analysis population, and any sensitivity checks. Those details are not reported in the registry record, and no conclusions about their impact can be drawn.

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: elective cardiac surgery (14.1%), pa band removal (7.6%), abnormal lab value (6.5%), elective procedure (6.5%), pneumonia (5.4%).

For the Muscular VSD Occluder group, the registry reports 51 participants with serious adverse events among 92 at risk, 17 participants with other adverse events among 92 at risk, and 2 deaths. These are descriptive counts. They do not indicate whether an event was caused by the device, the procedure, the underlying condition, or another factor; causal attribution is not reported in the registry record.

The listed serious event terms and percentages are elective cardiac surgery (14.1%), PA band removal (7.6%), abnormal lab value (6.5%), elective procedure (6.5%), pneumonia (5.4%), and elective surgery (4.3%). These terms describe events recorded in the registry; they are not a comparative risk estimate. The record does not specify the event-term counting rules, timing, or whether categories overlap, so the listed percentages should not be added together.

The safety group has no control arm. Consequently, these figures cannot show how event frequency compares with an untreated group or another treatment. The registry record also does not report detailed seriousness criteria, follow-up duration for the safety summaries, or relatedness assessments. Counts alone should not be interpreted as evidence for or against a causal relationship.

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

The record documents a post-approval study intended to further evaluate safety and effectiveness of the AMPLATZER Muscular VSD Occluder. It defines the primary effectiveness endpoint as successful device deployment during the procedure and identifies a prospective attempted-placement population, N=80. It also records safety summaries for the Muscular VSD Occluder group.

The primary technical-success result is not reported in the registry record. Therefore, the record does not show the observed success count or allow an assessment of its statistical precision. The endpoint definition explains what was intended to be measured, but a definition cannot stand in for an outcome estimate. The record also does not provide a target against which the result could be judged.

The safety counts and event terms describe what the registry records, but they do not establish that the device caused or prevented any event. With no comparator, the study cannot estimate a relative effect against another treatment. Nor do the posted counts alone separate events related to the device or procedure from those related to the participants' condition or other care.

These limitations do not erase the descriptive role of a post-approval study. Such records can contribute information about procedural experience and recorded events in the studied population. The strength of that information depends on complete outcome reporting, clear definitions, follow-up, and transparent analysis. Several of those details are not reported in the registry record.

Accordingly, the most defensible reading is narrow: the registry describes the study design, the intended technical-success endpoint, its analysis population, and selected safety counts. It does not report the primary effectiveness result or a comparative analysis. The record cannot support a conclusion about relative effectiveness, causality, or the precision of technical success.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and analysis populations are essential to interpreting a device study. Technical success is defined as successful deployment during the procedure, and the primary population is prospective participants with attempted placement, N=80. Those details identify the intended question more clearly than enrollment alone, which is recorded as 92.

It also illustrates the limits of single-group evidence. Without a concurrent comparator, observed outcomes can describe procedural experience but cannot directly estimate a treatment contrast. Safety counts are especially easy to overinterpret if they are treated as attributable effects rather than descriptive observations. The record's serious adverse event counts, other adverse event counts, and deaths require that distinction.

A further statistical lesson is that a clearly specified endpoint is not enough: the outcome estimate must also be available. The registry defines technical success but does not report its result. As a result, the primary effectiveness question cannot be answered from the registry record, and precision cannot be assessed. The absent result is a central reporting limitation, not a reason to infer success or failure.

Finally, prospective and retrospective enrollment are not interchangeable when selection depends on outcome knowledge. The record says retrospective enrollees were selected based on established technical success, while the primary effectiveness population includes prospective enrollees only. Reporting that distinction helps readers understand why the endpoint population is narrower than total enrollment and why the selection process deserves attention.

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 is that the registry record defines the technical-success endpoint but does not report its observed result. The success count, an uncertainty interval, and any benchmark comparison are therefore unavailable for interpretation. The record lists no analyses, so it does not provide a statistical estimate that could resolve this gap.

The study has a single-group design, with no concurrent comparator. It cannot estimate a relative treatment effect or distinguish the intervention's contribution from other factors. Masking is recorded as NONE, while details about outcome assessment procedures are not reported in the registry record.

The primary effectiveness population is prospectively enrolled participants with attempted placement, N=80, whereas enrollment is recorded as 92. The record says retrospective enrollees were selected based on established technical success, but the full explanation is incomplete. It does not provide enough detail to evaluate all selection processes or the outcome status of participants outside the primary population.

Other limitations include the absence of a reported sample-size justification, statistical analysis plan, missing-data approach, multiplicity strategy, confidence intervals, and interim-analysis information. Their status beyond what is recorded cannot be inferred. The registry also does not provide detailed safety-event definitions, timing, relatedness assessments, or the counting rules for listed serious event terms. These gaps limit interpretation of both effectiveness and safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Closure of Muscular Ventricular Septal Defects (VSDs) With the AMPLATZER Muscular VSD (MuVSD) Occluder - Post Approval Study — NCT00647387.
• Registry record last updated 2025-02-11; status last verified 2025-02.
• Results first posted 2025-02-07.
• 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

NCT00647387 is a completed, single-group post-approval study of the AMPLATZER Muscular VSD Occluder, sponsored by Abbott Medical Devices. The registry records enrollment of 92, study start 2008-03, and primary completion 2024-02-23. The study was designed to further evaluate safety and effectiveness in implanted subjects.

The primary endpoint is technical success during the procedure, defined as successful device deployment. Its stated population is prospectively enrolled participants with attempted placement, N=80. The registry record does not report the endpoint result and lists no analyses.

For the Muscular VSD Occluder group, the record reports 51 participants with serious adverse events among 92 at risk, 17 with other adverse events among 92 at risk, and 2 deaths. These are descriptive figures without a concurrent comparator or reported causal attribution.